CONTROL OF GONADOTROPIN SECRETION DURING LACTATION
M Susan Smith, Associate Professor Of Physiology
Oregon Health And Science University 3181 Sw Sam Jackson Pk Rd Portland, Or 972393098
Grant 2R01HD014643-19A1 from National Institute Of Child Health And Human Development IRG: REN
Abstract: The central hypothesis of this proposal is that the suppression of GnRH neuronal activity during lactation is due to neural impulses, derived from the suckling stimulus, that alter hypothalamic function and to the change in energy balance associated with milk production. We have identified specific areas in the brainstem that are activated by the suckling stimulus; neurons from each of these areas send projections to the arcuate nucleus of the hypothalamus. We also reported that several neuronal systems in the arcuate nucleus are altered during lactation (increased NPY and AGRP, decreased POMC). These changes are consistent with the chronic hyperphagia of lactation. Our studies showed that NPY projections from the arcuate nucleus makes direct contact with GnRH neurons in the preoptic area and with CRH neurons in the periventricular nucleus (a key site for regulation of food intake). Also, NPY receptors (Y5 subtype) are expressed on GnRH and CRH neurons. Thus, we have established the neuroanatomic framework by which increased NPY activity in the arcuate nucleus could serve as a key element in linking changes in energy balance to the suppression of GnRH neuronal activity during lactation. Another indicator of the change in energy balance is the suppression of leptin during lactation in association with milk production. The proposed experiments expand on these findings and will use three approaches 1) Neuroanatomical studies will determine the phenotypes of the suckling-activated brainstem neurons that make contact with NPY or POMC neurons in the arcuate nucleus and with GnRH neurons in the preoptic area. 2) Physiological studies will determine if the increase in NPY and the decrease in leptin play functional roles in the suppression of GnRH neuronal activity. 3) Functional genomics will be used to identify additional relevant genes that play key roles in the regulation of NPY and GnRH neurons and in conveying information about the state of energy balance during lactation. The interaction between reproductive function and energy balance during lactation provides a physiological model for studying a number of conditions in women (under-nutrition, anorexia nervosa, bulimia and exercise-induced amenorrhea) that involve a suppression of reproductive function associated with changes in energy balance. All of these conditions have common mechanisms underlying the decrease in GnRH activity.
Keywords: gonadotropin releasing factor, hormone regulation /control mechanism, lactation, neuroanatomy, neuron, neuropeptide Y, bioenergetics, brain stem, gene expression, hypothalamus, leptin, luteinizing hormone, phenotype, protein structure function, secretion, stimulus /response, confocal scanning microscopy, immunocytochemistry, immunofluorescence technique, in situ hybridization, injection /infusion, laboratory rat, microarray technology, radiotracer, tissue /cell culture
Project start date: 1979-12-01
Project end date: 2005-02-28
2R01HD014643-19A1 (2001): $248102
Sponsored Links Excellgen http://Excellgen.com
CONTROL OF GONADOTROPIN SECRETION DURING LACTATION
M Susan Smith, Associate Professor Of Physiology
University Of Pittsburgh At Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260
Grant 2R01HD014643-10A1 from National Institute Of Child Health And Human Development IRG: BCE
Abstract: The overall goal of this continuing research is to delineate the mechanisms involved in the suppression of gonadotropin secretion induced by the suckling stimulus. All of our data is consistent with the hypothesis that suckling greatly suppresses GnRH release from the hypothalamus leading to a decrease in pituitary gonadotropin function, as evidenced by a decrease in pituitary GnRH receptors, pituitary sensitivity to GnRH, LH submit mRNA and pulsatile LH secretion. Thus, this system provides an excellent model in which to study the mechanisms involved in the restoration of normal pituitary gonadotrope function from a physiologically suppressed state. The studies proposed will also attempt to identify the factors associated with lactation that are responsible for the suppression of GnRH secretion. The proposed experiments will examine the differential regulation of LH and FSH secretion by measuring LH and FSH subunit mRNA levels during lactation and after pup removal, and also will examine the effects of administration of pulsatile GnRH and estradiol and progesterone on gonadotrophin subunit mRNA levels. Studies will determine if factors other than suppressed GnRH secretion may play a role during lactation in the decrease in pituitary GnRH receptors and pituitary sensitivity to GnRH. Studies will also more clearly define the recovery process of GnRH secretion after pup removal by characterizing the pattern of LH secretion between 0 and 24hr after pup removal and will test the hypothesis that the pattern of GnRH recovery after pup removal consists of an early increase in basal secretion, which upregulates GnRH receptors, followed later by the superimposition of GnRH pulses, which initiates pulsatile LH secretion. Techniques will be developed to measure GnRH biosynthesis by using 3H-amino acids to label newly synthesized GnRH. It is hoped that changes in GnRH biosynthesis will serve as an indicator of changes in GnRH neuronal activity. Studies will determine whether factors involved in suckling-induced prolactin and oxytocin secretion, such as VIP, oxytocin, activin, and serotonin, may also mediate the suppression of GnRH secretion. Because our experiments have shown that suppression of GnRH secretion requires input from areas of the CNS outside the hypothalamus, and neural impulses from the suckling stimulus travel through the lower brainstem to reach the hypothalamus, experiments will be conducted to identify areas in the lower brainstem which are responsible for the inhibitory input which suppress GnRH secretion. These studies should provide new insights into the regulation of GnRH secretion and pituitary gonadotrope function, and thus may contribute to new approaches for contraception, to correct infertility problems, and to an understanding of the mechanisms participating in lactation amenorrhea.
Keywords: ENDOCRINOLOGY, HORMONAL REGULATION AND CONTROL (MECHANISMS), INFORMATION PROCESSING AND CONTROL (NEURAL), PITUITARY-DIENCEPHALON HORMONES, GONADOTROPINS REGULATING FACTORS, PITUITARY-DIENCEPHALON HORMONES, PROLACTIN, BENZOPYRROLES, SEROTONIN, BRAIN, BRAIN STEM, BRAIN, DIENCEPHALON, HYPOTHALAMUS, ENDOCRINOLOGY, HORMONES BIOSYNTHESIS, PEPTIDE-POLYPEPTIDE HORMONES BIOSYNTHESIS, ESTRATRIENE SERIES, ESTRADIOL, FERTILITY-INFERTILITY, SEX CYCLES, ESTRUS, NEUROENDOCRINE SYSTEMS, NUCLEIC ACIDS, MRNA, PITUITARY-DIENCEPHALON HORMONES, FSH, PITUITARY-DIENCEPHALON HORMONES, GONADOTROPINS, PITUITARY-DIENCEPHALON HORMONES, LH-ICSH, PITUITARY-DIENCEPHALON HORMONES, OXYTOCIN, PSYCHOLOGY, BEHAVIOR, SUCKING, RECEPTORS, HORMONE RECEPTORS, STIMULUS-RESPONSE, ANIMALS, CHORDATES, MAMMALS, RODENTS, MYOMORPHA, RATS (LABORATORY), CHEMISTRY, CLINICAL, BLOOD, RADIOISOTOPES, HYDROGEN, RADIOTRACERS, TISSUE (CELL) CULTURE, ORGAN CULTURE
Project start date: 1979-12-01
Project end date: 1994-03-31
2R01HD014643-23A2 (2006): $304403
2R01HD014643-15A2 (1996): $232492
Grants awarded to M Susan Smith
CONTROL OF GONADOTROPIN SECRETION DURING LACTATION
M Susan Smith
Oregon Health And Science University, 3181 Sw Sam Jackson Pk Rd, Portland, Or 97239-3098
Abstract: This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Lactation is characterized by an inhibition of reproductive cyclicity due to a suppression of gonadotropin releasing hormone (GnRH), excessive hyperphagia and negative energy balance due to milk production. The central hypothesis of this proposal is that suppression of GnRH/LH secretion is due to suckling-induced alterations in hypothalamic neural systems that regulate food intake and energy balance. Our studies have recently established that several hypothalamic neuropeptide orexigenic systems involved in regulating food intake/energy balance (NPY, orexin, melanin concentrating hormone) make direct connections with GnRH neurons, thus providing a neuroanatomical framework by which signals denoting changes in food intake/energy balance can be directly transmitted to GnRH neurons. We have also found changes in a number of substances that reflect the negative energy balance (suppressed leptin, insulin) and are likely to be involved in the chronic hyperphagia during lactation, a condition similar to obesity. Current studies are using hypothalamic explants and electrophysiology to determine if NPY, orexin or melanin concentrating hormone have direct inhibitory effects on GnRH neurons. Studies are also restoring leptin and insulin to postlactation levels and determining the effects on hypothalamic neuropeptide feeding systems and on restoration of GnRH/LH secretion. The interaction between reproductive function and energy balance during lactation provides a physiological model for studying a number of conditions in women (undernutrition, anorexia nervosa, bulimia and exercise-induced amenorrhea) that involve a suppression of reproductive function associated with changes in energy balance. The results of the studies in the rat formed the basis of a new funded project to study control of food intake in the rhesus monkey
Keywords: Amenorrhea; Anorexia Nervosa; CRISP; Cell Communication and Signaling; Cell Signaling; Chronic; Common Rat Strains; Computer Retrieval of Information on Scientific Projects Database; Controlled Study; Cyclicity; D-His-6-Pro-8-NEt-LHRH; Eating; Electrophysiology; Electrophysiology (science); Exercise; Exercise, Physical; FSH-Releasing Hormone; Food Intake; Funding; GnRH (gonadotropin releasing hormone); Gonadoliberin; Gonadorelinum; Gonadotropin Hormone Releasing Hormone; Gonadotropin-Releasing Hormone; Gonadotropins; Grant; Hcrt protein; Hcrt/ORX; Hcrts/ORXs; Hoe- 471; Humulin R; Hyperphagia; Hypothalamic structure; Hypothalamus; Institution; Insulin; Insulin (ox), 8A-L-threonine-10A-L-isoleucine-30B-L-threonine-; Insulin, Regular; Intracellular Communication and Signaling; Investigators; LH-FSH Releasing Hormone; LH-Releasing Hormone; LHFSH Releasing Hormone; Lactation; Leptin; Luliberin; Luteinizing Hormone-Releasing Factor; Luteinizing Hormone-Releasing Hormone; Luteinizing hormone-releasing factor (pig); Macaca mulatta; Malnutrition; Mammals, Primates; Mammals, Rats; Milk; NIH; National Institutes of Health; National Institutes of Health (U.S.); Nerve Cells; Nerve Unit; Nervosas, Anorexia; Nervous; Neural Cell; Neurocyte; Neurons; Neuropeptides; Neurophysiology / Electrophysiology; Novolin R; Nutritional Deficiency; Ob Gene Product; Ob Protein; Obese Gene Product; Obese Protein; Obesity; Overeating; Periodicity; Physiologic; Physiological; Primates; Production; Pulsti; Rat; Rattus; Recombinant Gonadorelin; Research; Research Personnel; Research Resources; Researchers; Resources; Rhesus; Rhesus Macaque; Rhesus Monkey; Rhythmicity; Signal Transduction; Signal Transduction Systems; Signaling; Source; Study models; System; System, LOINC Axis 4; Therapeutic GRH; Undernutrition; United States National Institutes of Health; Woman; adiposity; amenia; base; biological signal transduction; corpulence; corpulency; corpulentia; dietary deficiency; energy balance; feeding; follicle stimulating hormone-releasing factor; gonadotropin releasing factor; hypocretin; hypocretin/orexin; hypocretins/orexins; hypothalamic; melanin-concentrating hormone; melanophore-concentrating hormone; melanosome concentrating hormone; neural; neuronal; ob/ob mouse; obese; obese people; obese person; obese population; orexin; polyphagia; relating to nervous system; reproductive; reproductive function; restoration
Project start date: 2009-08-04
Project end date: 2010-04-30
Budget start date: 4-AUG-2009
Budget end date: 30-APR-2010
2P51RR000163-50_8604 (2009): $80343
AIDS-related Animal Services Building Cage Washing Facility
M Susan Smith, Associate Professor Of Physiology
Oregon Health And Science University 3181 Sw Sam Jackson Pk Rd Portland, Or 972393098
Grant 1G20RR023957-01 from National Center For Research Resources IRG: STRB
Abstract: This proposal requests funds to renovate the old cage washing facility in the original part of the Animal Services Building (ASB) complex that houses nonhuman primates (NHPs). Our objectives are to provide outstanding animal care for NHPs by maintaining the highest levels of sanitation and complying with USDA regulations and AAALAC guidelines. The need to renovate the old cage wash facility is driven by growing research programs at ONPRC. Much of this growth has been in AIDS-related and other infectious disease projects. To support these projects, the ONPRC has greatly expanded its SPF and expanded SPF-lndian-origin rhesus macaque populations. An increase in cage wash sanitation capabilities will insure successful growth of this valuable colony while preventing contamination of viruses that confound AIDS-related research. In addition, most of the NHPs involved in AIDS-related research are housed in the original part of the ASB and are dependent on the old cage washing facility for NHP cage sterilization and sanitation. This facility has been in service for over 15 years, and it has had increasing use as the number of animals assigned to projects has increased and as the ASB complex has expanded. Fifteen years of very heavy use have resulted in significant deterioration of all mechanical systems of the cage washer. There have been numerous mechanical malfunctions in the last 4 years, resulting in very poor reliability. Thus, a new cage washer is a critical piece of equipment that would provide reliable service for at least another 15-20 years. In addition, the old cage washer is only a single-sided machine, which limits the through-put of cages and restricts the number of animals that can be housed in the ASB without running additional shifts. The proposed purchase of a new, more reliable cage washer that has double the capacity of the current 15-year-old machine would allow ONPRC to continue to expand the use of NHPs, provide back-up capabilities for other cage washers, facilitate compliance with USDA regulations that require cage sanitation at least every 2weeks, and conserve natural and financial resources through improved operating efficiency. We also propose to refurbish drains and wall and floor surfaces throughout the cage washing facility; these upgrades will improve room sanitation levels, create durable finishes that will insure USDA compliance for the long-term, improve efficiency, and provide for a much safer work environment for employees. The following aims are proposed in this grant Specific Aim 1 Purchase a Lynx Model 450LX Rack and Cage Washer, double wide. Specific Aim 2 Remodel the site for installation of the double-wide cage washer and refurbish the drains, floors and walls throughout the cage washing facility.
Keywords: AIDS, housing, Macaca, Primate, animal care, animal colony, back, behavior test, communicable disease, cooperative study, employee, ethology, gait, health, model, motivation, vaccine development, virus, work site
Project start date: 2007-05-21
Project end date: 2009-05-20
1G20RR023957-01 (2007): $536461
CONTROL OF GONADOTROPIN SECRETION DURING LACTATION
M Susan Smith, Associate Professor Of Physiology
Oregon Health And Science University 3181 Sw Sam Jackson Pk Rd Portland, Or 972393098
Grant 5P51RR000163-430010 from National Center For Research Resources
Abstract: The reproductive state of lactation, which occurs in all mammals, is associated with an inhibition of reproductive cyclicity and ovulation due to a suppression of gonadotropin releasing hormone (GnRH), the hypothalamic neuroendocrine neurons regulating reproduction. The focus of our studies is to identify the afferent neuronal pathways activated during lactation by the suckling stimulus that are responsible for the suppression of GnRH neuronal function. This past year, we made the following observations 1) Using neuronal tract tracing techniques and confocal microscopy, we have shown that NPY neurons activated by the suckling stimulus project to areas containing GnRH neurons and make contact with GnRH neuronal processes. These results suggest a possible neuronal mechanism by which suckling inhibits GnRH neuronal activity. 2) The large increase in food intake during lactation most likely occurs in response to substances that signal changes in metabolic activit y, such as leptin (a satiety-inducing substance) and agouti-related transcript (ART, induces obesity). During lactation, blood leptin levels are greatly suppressed, whereas ART expression is increased in the hypothalamus. Current studies in the laboratory are examining the relationship between the changes in leptin and ART and the increase in NPY neuronal activity and food intake. In addition, we are exploring possible interactions between the regulation of food intake and of gonadotropin releasing hormone neuronal activity during lactation. It is well established that many causes of infertility are related to changes in energy homeostasis, such as in exercised-induced amenorrhea and anorexia nervosa. An understanding of the mechanisms by which the suckling stimulus imposes an inhibition on GnRH neuronal function provides information that is relevant to primates (including humans), in which the reproductive neuroendocrine axis regulating ovarian cyclicity is also inhibited. These studies have relevance to women s reproductive health as they will increase our understanding of hypothalamic causes of infertility and provide new approaches for contraception. FUNDING NIH HD14643 PUBLICATIONS Li C, Chen P, Smith MS. The acute suckling stimulus induces expression of Neuropeptide Y (NPY) in cells in the dorsomedial hypothalamus and increases NPY expression in the arcuate nucleus. Endocrinology 1391645-1652, 1998. Li C, Chen P, Smith MS. Neuropeptide Y (NPY) neurons in the arcuate nucleus (ARH) and dorsomedial nucleus (DMH), areas activated during lactation, project to the paraventricular nucleus of the hypothalamus (PVH). Reg Peptides 75-7693-100, 1998. Li C, Chen P, Smith MS. Neuropeptide Y (NPY) and tuberinfundibular dopamine (TIDA) are altered during lactation role of prolactin. Endocrinology 140 118-123,1999. Grove KL, Smith MS. Resistance of the hippocampus in the lactating rat to N-methyl-D-aspartate (NMDA)-mediated excitation is not due to a nonfunctional receptor system. Brain Res 814157-163, 1998. Grove KL, Smith MS. 3?-hydroxysteroid dehydrogenase (3? -HSD) and mRNA distribution in the rat brain. In The Endocrine Society Program and s 80th Annual Meeting (held in New Orleans, LA, June 24-27, 1998), p 493 ( #P3-527). Brogan RS, Kuper J, Duncan JS, Trayhurn P, Smith MS. Serum leptin levels during lactation are related to the metabolic drain of milk projection lack of correlation to serum LH. In The Endocrine Society Program and s 80th Annual Meeting (held in New Orleans, LA, June 24-27, 1998), p 349 ( #P2-478). Chen P, Haskell-Luevano C, Cone RD, Smith MS. Coexpression of agouti-related transcript (ART) and neuropeptide Y (NPY) in the hypothalamic arcuate nucleus of female rats during the estrous cycle and lactation. In the Endocrine Society Program and s 80th Annual Meeting (held in New Orleans, LA, June 24-27, 1998), p 521 ( #P3-663). Li C, Chen P, Smith MS. Anatomical interactions between neuropeptide Y neurons from arcuate nucleus of the hypothalamus (ARH-NPY) and the gonadotropin-releasing hormone (GnRH) in the hypothalamus. In The Endocrine Society Program and s 80th Annual Meeting (held in New Orleans, LA, June 24-27, 1998), p 59 ( #OR5-5). Li C, Chen P, Smith MS. Neuropeptide Y neurons from the arcuate nucleus of the hypothalamus (ARH-NPY) directly project to corticotropin releasing hormone (CRF) neurons in the paraventricular nucleus (PVH). Soc Neurosci Abstr 24(pt 1)369, 1998 ( #146.8). Brogan RS, Grove KL, Smith MS. Leptin receptor expression during lactation. Society for the Study of Reproduction 58(suppl 1)96 ( #81).
Keywords: endocrine gland /system, ethics, hormone, mother /infant health care, nervous system, reproductive system, women s health, Mammalia, clinical research
M Susan Smith, Associate Professor Of Physiology
Oregon Health And Science University 3181 Sw Sam Jackson Pk Rd Portland, Or 972393098
Grant 1G20RR018326-01 from National Center For Research Resources IRG: STRB
Abstract: The renovation project is part of a long-range plan to expand rhesus macaque (Macaca mulatta) production at the ONPRC. The specific aim of this application is to alter and renovate the 30-year-old facilities associated with six one-acre corrals that hold SPF Indian rhesus macaque breeding colonies. The continued use of the corrals for rhesus macaque production is driven by the following 1) the growth in research projects and the numbers of NHPs assigned to projects requires a substantial increase in the number of available NHPs; 2) the ONPRC is a national resource and must provide accessibility to investigators outside of the Center; 3) the long-range plan calls for the doubling of SPF breeding program to create a self-sustaining supply of NHPs; 4) the reserve capacity for animal housing must be expanded for proper animal management; and 5) the corrals are a cost effective method for breeding and raising animals into adulthood in a complex and environmentally rich social structure. Animals in the corrals are used as juveniles (research programs in AIDS, infectious diseases, developmental neurobiology), adults (research programs in immunology, neuroscience and reproduction) and retired breeders (research programs in aging). The renovation of the corral facilities will make them suitable for long-term use and includes the following 1) convert the storage area between corrals four and five into a sheltered feeding area for corral five; 2) convert the existing corral five feeding area into an area for safe handling of animals; 3) upgrade the infrastructure (electric service, domestic water, sanitary sewer) for all rhesus corral facilities; 4) replace the deteriorated roofs on all feeding and holding areas; 5) replace damaged and worn metal panels on all structures; 6) repair and reseal concrete in all feeding and holding areas; 7) install additional radiant heaters and lights in all feeding and holding areas; 8) install a water pressure booster pump for wash down systems; 9) add perching to all feeding areas; and 10) replace deteriorating animal enrichment equipment in all corrals. This application will provide funds for the renovation of facilities associated with six one-acre corrals. The renovation is necessary for continued use of the corrals to expand rhesus macaque production and to comply with United States Department of Agriculture (USDA) policies and provisions of the Animal Welfare Act (AWA).
Keywords: Macaca mulatta, animal colony, building /facility design /renovation, animal breeding, animal care
Project start date: 2003-02-01
Project end date: 2007-01-31
1G20RR018326-01 (2003): $700000
CONTROL OF GONADOTROPIN SECRETION DURING LACTATION
M Susan Smith, Associate Professor Of Physiology
University Of Pittsburgh At Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260
Grant 5R01HD014643-13 from National Institute Of Child Health And Human Development IRG: BCE
Abstract: The overall goal of this continuing research is to delineate the mechanisms involved in the suppression of gonadotropin secretion induced by the suckling stimulus. All of our data is consistent with the hypothesis that suckling greatly suppresses GnRH release from the hypothalamus leading to a decrease in pituitary gonadotropin function, as evidenced by a decrease in pituitary GnRH receptors, pituitary sensitivity to GnRH, LH submit mRNA and pulsatile LH secretion. Thus, this system provides an excellent model in which to study the mechanisms involved in the restoration of normal pituitary gonadotrope function from a physiologically suppressed state. The studies proposed will also attempt to identify the factors associated with lactation that are responsible for the suppression of GnRH secretion. The proposed experiments will examine the differential regulation of LH and FSH secretion by measuring LH and FSH subunit mRNA levels during lactation and after pup removal, and also will examine the effects of administration of pulsatile GnRH and estradiol and progesterone on gonadotrophin subunit mRNA levels. Studies will determine if factors other than suppressed GnRH secretion may play a role during lactation in the decrease in pituitary GnRH receptors and pituitary sensitivity to GnRH. Studies will also more clearly define the recovery process of GnRH secretion after pup removal by characterizing the pattern of LH secretion between 0 and 24hr after pup removal and will test the hypothesis that the pattern of GnRH recovery after pup removal consists of an early increase in basal secretion, which upregulates GnRH receptors, followed later by the superimposition of GnRH pulses, which initiates pulsatile LH secretion. Techniques will be developed to measure GnRH biosynthesis by using 3H-amino acids to label newly synthesized GnRH. It is hoped that changes in GnRH biosynthesis will serve as an indicator of changes in GnRH neuronal activity. Studies will determine whether factors involved in suckling-induced prolactin and oxytocin secretion, such as VIP, oxytocin, activin, and serotonin, may also mediate the suppression of GnRH secretion. Because our experiments have shown that suppression of GnRH secretion requires input from areas of the CNS outside the hypothalamus, and neural impulses from the suckling stimulus travel through the lower brainstem to reach the hypothalamus, experiments will be conducted to identify areas in the lower brainstem which are responsible for the inhibitory input which suppress GnRH secretion. These studies should provide new insights into the regulation of GnRH secretion and pituitary gonadotrope function, and thus may contribute to new approaches for contraception, to correct infertility problems, and to an understanding of the mechanisms participating in lactation amenorrhea.
Keywords: gonadotropin releasing hormone, hormone regulation /control mechanism, neural information processing, prolactin, brain stem, estradiol, estrus, follicle stimulating hormone, gonadotropin, hormone receptor, hypothalamus, luteinizing hormone, messenger RNA, neuroendocrine system, oral behavior, oxytocin, peptide hormone biosynthesis, serotonin, stimulus /response, blood chemistry, laboratory rat, organ culture, radiotracer, tritium
Project start date: 1979-12-01
Project end date: 1994-06-30
5R01HD014643-13 (1993): $151216
5R01HD014643-12 (1992): $145038
Sponsored Links Excellgen http://Excellgen.com
A BSL3 Facility For AIDS-Related Research
M Susan Smith, Associate Professor Of Physiology
Oregon Health And Science University 3181 Sw Sam Jackson Pk Rd Portland, Or 972393098
Grant 1G20RR021376-01 from National Center For Research Resources IRG: STRB
Abstract: The Oregon National Primate Research Center (ONPRC) seeks funds to complete the second phase of a two-phase process of converting the Kroc quarantine building (Kroc) to an ABSL 3 facility. This facility will be used for Acquired Immune Deficiency Syndrome (AIDS)-related research using pathogens with aerosol transmission potential and for international quarantine of imported nonhuman primates (NHPs). Our longterm objectives are to 1) provide ABSL 3 NHP housing facilities suitable for AIDS-related research; 2) protect immunodeficient NHPs used in other AIDS-related research; and 3) improve facilities for international quarantine of imported NHPs. The Kroc quarantine facility has been designated for international quarantine and ABSL 3 projects. The first phase of converting the Kroc to an ABSL 3 facility was completed August 2003. The second phase, requested in this application, will be accomplished with two specific aims. Specific Aim 1 proposes to purchase fixed and movable equipment for inclusion in the Kroc ABSL 3 facility (i.e., a pass-thru autoclave, redundant HVAC supply and exhaust equipment, an effluent kill tank, a downdraft necropsy table, a biosafety cabinet, a portable radiograph machine, an automatic x-ray film processor, and other miscellaneous equipment). Specific Aim 2 proposes alterations and renovations of the Kroc with installation of the purchased equipment to complete the conversion to an ABSL 3 facility.
Keywords: AIDS, animal colony, biomedical equipment purchase, biomedical facility, building /facility design /renovation, veterinary science, HIV infection, animal care, communicable disease control, isolation /quarantine, Primate
Project start date: 2005-05-16
Project end date: 2008-05-31
1G20RR021376-01 (2005): $640000
Nonhuman Primate Primary Housing Units For Animal Services Building 3
M Susan Smith, Associate Professor Of Physiology
Oregon Health And Science University 3181 Sw Sam Jackson Pk Rd Portland, Or 972393098
Grant 1G20RR022759-01 from National Center For Research Resources IRG: STRB
Abstract: The ONPRC requests funds to purchase primary housing units (cages and racks), psychological enrichment devices (play pens, porches and tunnels) and other related equipment used in housing non-human primates (NHPs). Our objectives are to provide housing for NHPs involved in NIH-sponsored AIDS-related research. The primary housing units will be installed in a newly constructed animal housing and support facility called Animal Services Building 3 (ASB3, approximately 35,000 sq. ft). With the expansion of research programs and the number of NHPs assigned to research projects, the need for NHP housing at the ONPRC has continued to grow. The ONPRC has been successful in obtaining NIH construction grants and institutional funds to greatly expand its animal housing facilities. ASB3 is the third addition to the original ASB and will add an additional 900 housing spaces for NHPs in cages and small group housing units. Many of the animals to be housed in ASB3 will be used in support of our AIDS-related research program. Our SPF Indian-orgin rhesus breeding colony has reached 2,060 NHPs and the expanded SPF program continues to grow. These animals are used in the infectious disease and immunology studies, and many will be housed in ASB3. In order to continue to expand our AIDS-related research programs, it is essential that sufficient cage space be available. The primary housing units requested in this proposal will allow the ONPRC to fully occupy the new ASB3 facility and house SPF NHPs under state-of-the-art conditions in an enhanced social environment. The ONPRC has been at the forefront in increasing the social environment of NHPs housed at the Center. The awarding of this G20 application will allow the ONPRC to have approximately 90% of the entire NHP colony in an enhanced social environment. The following aims are proposed in this grant Specific Aim 1 Purchase 50 mobile stainless steel racks designed to hold four 4.5 sq. ft. cages each (200 total cages). Specific Aim 2 Purchase equipment to enrich the social environment, including mobile play pens for group housing, and tunnels and porches that attach to the cages. Specific Aim 3 Purchase additional equipment, including transfer boxes and capture tunnels for moving monkeys between cages or playpens, and blood collection stations.
Keywords: Primate, housing
Project start date: 2006-06-01
Project end date: 2008-05-31
1G20RR022759-01 (2006): $410850
M Susan Smith, Associate Professor Of Physiology
Oregon Health And Science University 3181 Sw Sam Jackson Pk Rd Portland, Or 972393098
Grant 1G20RR018457-01 from National Center For Research Resources IRG: STRB
Abstract: The ONPRC proposes to purchase caging suitable for housing SPF male Indian-origin rhesus macaques (Macaca mulatta) used in AIDS related research. Increasing demands for SPF rhesus macaques for AIDS related research at the ONPRC and nationally has exceeded the supply efforts to expand production colonies to supply more animals has necessitated retention of female offspring for breeding, leaving male SPF rhesus macaques as the primary model for AIDS-related research projects. The Animal Biosafety Level 2 and 3 (ABLS2 and ABSL3) containment facility which houses animals for AIDS-related research at the ONPRC is not equipped with cages suitable for Group 4 male rhesus macaques. The existing cages do not have the 6.0 sq. ft. of floor space required by USDA and do not provide the option of social housing. It is very important that animals used in AIDS-related research have the opportunity to experience an enriched social environment. Requested in this application are 6.2 sq. ft. cages and associated equipment that will comply with USDA requirements for Group 4 male rhesus macaques and provide a wide range of options for environmental enrichment and social housing of NHPs used in AIDS-related research.
Keywords: AIDS, Macaca mulatta, animal care, animal colony, biomedical equipment purchase
Project start date: 2003-02-01
Project end date: 2007-01-31
1G20RR018457-01 (2003): $700000
CONTROL OF GONADOTROPIN SECRETION DURING LACTATION
M Susan Smith, Associate Professor Of Physiology
Oregon Health And Science University 3181 Sw Sam Jackson Pk Rd Portland, Or 972393098
Grant 5R01HD014643-22 from National Institute Of Child Health And Human Development IRG: REN
Abstract: The central hypothesis of this proposal is that the suppression of GnRH neuronal activity during lactation is due to neural impulses, derived from the suckling stimulus, that alter hypothalamic function and to the change in energy balance associated with milk production. We have identified specific areas in the brainstem that are activated by the suckling stimulus; neurons from each of these areas send projections to the arcuate nucleus of the hypothalamus. We also reported that several neuronal systems in the arcuate nucleus are altered during lactation (increased NPY and AGRP, decreased POMC). These changes are consistent with the chronic hyperphagia of lactation. Our studies showed that NPY projections from the arcuate nucleus makes direct contact with GnRH neurons in the preoptic area and with CRH neurons in the periventricular nucleus (a key site for regulation of food intake). Also, NPY receptors (Y5 subtype) are expressed on GnRH and CRH neurons. Thus, we have established the neuroanatomic framework by which increased NPY activity in the arcuate nucleus could serve as a key element in linking changes in energy balance to the suppression of GnRH neuronal activity during lactation. Another indicator of the change in energy balance is the suppression of leptin during lactation in association with milk production. The proposed experiments expand on these findings and will use three approaches 1) Neuroanatomical studies will determine the phenotypes of the suckling-activated brainstem neurons that make contact with NPY or POMC neurons in the arcuate nucleus and with GnRH neurons in the preoptic area. 2) Physiological studies will determine if the increase in NPY and the decrease in leptin play functional roles in the suppression of GnRH neuronal activity. 3) Functional genomics will be used to identify additional relevant genes that play key roles in the regulation of NPY and GnRH neurons and in conveying information about the state of energy balance during lactation. The interaction between reproductive function and energy balance during lactation provides a physiological model for studying a number of conditions in women (under-nutrition, anorexia nervosa, bulimia and exercise-induced amenorrhea) that involve a suppression of reproductive function associated with changes in energy balance. All of these conditions have common mechanisms underlying the decrease in GnRH activity.
Keywords: gonadotropin releasing factor, hormone regulation /control mechanism, lactation, neuroanatomy, neuron, neuropeptide Y, bioenergetics, brain stem, gene expression, hypothalamus, leptin, luteinizing hormone, phenotype, protein structure function, secretion, stimulus /response, confocal scanning microscopy, immunocytochemistry, immunofluorescence technique, in situ hybridization, injection /infusion, laboratory rat, microarray technology, radiotracer, tissue /cell culture
Project start date: 1979-12-01
Project end date: 2006-06-30
5R01HD014643-22 (2004): $248102
5R01HD014643-21 (2003): $248102
5R01HD014643-20 (2002): $248102
5R01HD014643-27 (2010): $282754
5R01HD014643-26 (2009): $285611
3R01HD014643-26S1 (2009): $178291
5R01HD014643-25 (2008): $285611
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5R01HD014643-24 (2007): $297388
5R01HD014643-18 (1999): $242817
5R01HD014643-17 (1998): $236268
5R01HD014643-16 (1997): $221825
Sponsored Links Excellgen http://Excellgen.com