The long-term objectives are to determine whether hypothalamic control of GRF and SRIF involves self-regulation (ultrashort-loop feedback) of each of these neuropeptides on its own neurosecretion and/or the action of each of these neurohormones to regulate the hypothalamic release of the other, and to establish what the implications of such control systems are for the regulation of pulsatile GH release. Since hypothalamic dysfunction has been implicated in GH deficiency and short stature and could be involved in gigantism and acromegaly, it is pertinent to examine possible mechanisms of autoregulation and reciprocal control of GRF and SRIF since disruption of these could function in disordered GH secretion.
The specific aims proposed to accomplish this are: 1. to determine in which hypothalamic nuclei administered GRF and SRIF are active to alter pulsatile GH secretion and whether these nuclei correspond to areas containing GRF and SRIF neuronal elements; 2. to collect information on the physiological function of GRF and SRIF autoregulation or reciprocal control in pulsatile GH secretion by using a SRIF antagonist and GRF and SRIF antisera for passive immunoneutralization studies; 3. to generate GRF and SRIF antisera in rabbits for the establishment of GRF and SRIF radioimmunoassays, for passive immunoneutralization studies, and for immunohistochemistry; 4. to determine whether administered GRF and SRIF have direct actions on their own release and/or on the release of each other by using the superfusion of hypothalamic slices and median eminences; 5. to determine effects of administered GRF and SRIF on the hypothalamus of the monosodium-glutamate-treated, GRF-deficient rat and the implications for pulsatile Gh release; 6. to observe the anatomical associations of GRF and SRIF neuronal elements at the light microscopic level to underpin the in vivo and in vitro findings of specific aims 1-5 above.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS023036-03
Application #
3406021
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1986-03-01
Project End
1989-02-28
Budget Start
1988-03-01
Budget End
1989-02-28
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Georgetown University
Department
Type
School of Medicine & Dentistry
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057
Mulroney, S E; McDonnell, K J; Pert, C B et al. (1998) HIV gp120 inhibits the somatotropic axis: a possible GH-releasing hormone receptor mechanism for the pathogenesis of AIDS wasting. Proc Natl Acad Sci U S A 95:1927-32
Peisen, J N; McDonnell, K J; Mulroney, S E et al. (1995) Endotoxin-induced suppression of the somatotropic axis is mediated by interleukin-1 beta and corticotropin-releasing factor in the juvenile rat. Endocrinology 136:3378-90
Haramati, A; Lumpkin, M D; Mulroney, S E (1994) Early increase in pulsatile growth hormone release after unilateral nephrectomy in adult rats. Am J Physiol 266:F628-32
Mulroney, S E; Lumpkin, M D; Roberts Jr, C T et al. (1992) Effect of a growth hormone-releasing factor antagonist on compensatory renal growth, insulin-like growth factor-I (IGF-I), and IGF-I receptor gene expression after unilateral nephrectomy in immature rats. Endocrinology 130:2697-702
Mulroney, S E; Lumpkin, M D; Haramati, A (1991) Suppression of growth hormone release restores phosphaturic response to PTH in immature rats. Am J Physiol 261:F1110-3
Lumpkin, M D; McDonald, J K (1989) Blockade of growth hormone-releasing factor (GRF) activity in the pituitary and hypothalamus of the conscious rat with a peptidic GRF antagonist. Endocrinology 124:1522-31
McDonald, J K; Lumpkin, M D; DePaolo, L V (1989) Neuropeptide-Y suppresses pulsatile secretion of luteinizing hormone in ovariectomized rats: possible site of action. Endocrinology 125:186-91
Mulroney, S E; Lumpkin, M D; Haramati, A (1989) Antagonist to GH-releasing factor inhibits growth and renal Pi reabsorption in immature rats. Am J Physiol 257:F29-34
Lumpkin, M D; Mulroney, S E; Haramati, A (1989) Inhibition of pulsatile growth hormone (GH) secretion and somatic growth in immature rats with a synthetic GH-releasing factor antagonist. Endocrinology 124:1154-9