Many of the basic physiological actions of growth hormone- releasing hormone (GHRH) have been investigated since its discovery approximately three years ago. Yet the use of GHRH to enhance growth in humans and other species, while successful and very exciting, has proven to be very laborious and at present holds little practical application. This situation can be greatly improved by developing a clear understanding of the basic mechanisms regulating the secretion of GHRH and which factors impinge on its actions. The experiments proposed in this grant are designed to investigate many of these aspects.
Specific aims are 1) to establish the participating factors involved in the regulation of GHRH and somatostatin secretion, 2) to establish the role and significance of adrenal and gonadal steroids and thyroid hormone on the GHRH-GH neuroendocrine pathways, 3) evaluate the biological activity of agonists and antagonists of GHRH in vivo and 4) evaluate the metabolism of these GHRH analogues and GHRH itself.
These aims will be attained using a variety of in vivo methods. Specifically cerebral spinal fluid collection and hypothalamic-hypophyseal portal blood collection will be used to investigate the mechanisms involved in regulating hypothalamic GHRH and somatostatin secretion. The metabolism of GHRH and how steroid and thyroid hormones modulate the actions of GHRH will be investigated using conscious, freely- moving rats prepared with indwelling venous catheters. The development of a basic knowledge and understanding of the fundamental relationships between GHRH, somatostatin and GH will facilitate the successful use of GHRH on a clinical level to treat growth hormone related disorders and on an agricultural level to enhance growth and foodstuffs utilization. These activities are consistent with my long-term objectives to characterize the physiological relationship between GHRH and GH as it relates to normal growth and development. These objectives range from the neuronal level, e.g., establishing which central nervous system pathways are involved in regulating GHRH secretion, to the environmental level, e.g., establishing the role of GHRH and GH during the period of catch-up growth which occurs following the removal of animals from a food deprivation environment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK038324-03
Application #
3237653
Study Section
Endocrinology Study Section (END)
Project Start
1988-09-01
Project End
1993-08-31
Budget Start
1990-09-01
Budget End
1993-08-31
Support Year
3
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Wisconsin Milwaukee
Department
Type
Schools of Allied Health Profes
DUNS #
City
Milwaukee
State
WI
Country
United States
Zip Code
53201
Brogan, R S; Fife, S K; Conley, L K et al. (1997) Effects of food deprivation on the GH axis: immunocytochemical and molecular analysis. Neuroendocrinology 65:129-35
Fife, S K; Brogan, R S; Giustina, A et al. (1996) Immunocytochemical and molecular analysis of the effects of glucocorticoid treatment on the hypothalamic-somatotropic axis in the rat. Neuroendocrinology 64:131-8
Giustina, A; Wehrenberg, W B (1995) Influence of thyroid hormones on the regulation of growth hormone secretion. Eur J Endocrinol 133:646-53
Giustina, A; Misitano, V; Voltz, D et al. (1995) Adrenergic and cholinergic involvement in basal and growth hormone-releasing hormone-stimulated growth hormone secretion in glucocorticoid-treated rats. Endocr Res 21:719-32
Giustina, A; Voltz, D M; Teik, J et al. (1995) Galanin counteracts the inhibitory effects of glucocorticoids on growth hormone secretion in the rat. Metabolism 44:224-7
Butkus, J A; Brogan, R S; Giustina, A et al. (1995) Changes in the growth hormone axis due to exercise training in male and female rats: secretory and molecular responses. Endocrinology 136:2664-70
Voltz, D M; Piering, A W; Magestro, M et al. (1995) Effect of GHRP-6 and GHRH on GH secretion in rats following chronic glucocorticoid treatment. Life Sci 56:491-7
Gruaz, N M; Arsenijevic, Y; Wehrenberg, W B et al. (1994) Growth hormone (GH) deprivation induced by passive immunization against rat GH-releasing factor does not disturb the course of sexual maturation and fertility in the female rat. Endocrinology 135:509-19
Locatelli, V; Grilli, R; Torsello, A et al. (1994) Growth hormone-releasing hexapeptide is a potent stimulator of growth hormone gene expression and release in the growth hormone-releasing hormone-deprived infant rat. Pediatr Res 36:169-74
Janowski, B A; Ling, N C; Giustina, A et al. (1993) Hypothalamic regulation of growth hormone secretion during food deprivation in the rat. Life Sci 52:981-7

Showing the most recent 10 out of 27 publications