The modulatory role of gonadal steroids in regulating sex- dependent growth hormone (GH) secretion will be studied during development through reproductive senescence. A series of interrelated experimental approaches will be used to clarify the level of gonadal steroid control of GH secretion (hypothalamic, pituitary and peripheral organs). In the course of these studies, GH secretory patterns throughout life in the rat will be defined. We anticipate that the results of these studies will advance our understanding of the development and maintenance of GH secretory dynamics and help explain sex-related differences in growth rates. The first series of experiments will define both a dose-response and time course for gonadal steroid action on GH secretory patterns using a chronically-cannulated rate in vivo model. Direct pituitary effects of steroids will be assessed by observing the GH response to GH-relating factor (GRF). A second series of experiments will investigate the hypothesis that gonadal steroids modulate GH secretion via a novel mechanism termed a """"""""steroid sensitive switch"""""""". The existence of the """"""""steroid sensitive switch"""""""" in adult rats will be studied by utilizing a paradigm involving the exposure of male and female rats to alternating courses of steroids. In addition, the development of the """"""""steroid sensitive switch"""""""" will be studied beginning with gestational life through adulthood. A third series of experiments will focus on GH secretory patterns throughout the life of male and female rats. Studies will investigate GH secretory patterns during puberty, during the estrous cycle in adult female rats and during various stages of reproductive senescence in both male and female rats. Studies will extend to investigating GRF-induced GH secretion during these various stages of life. Finally, the metabolic clearance rate and half-life components of GH in male and female rats will be determined to establish whether gonadal steroids play a role in modulating these parameters.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD022199-03
Application #
3321632
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1987-04-01
Project End
1991-03-31
Budget Start
1989-04-01
Budget End
1991-03-31
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Florida
Department
Type
Schools of Pharmacy
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Simpkins, J W; Millard, W J; Berglund, L A (1993) Effects of chronic stimulation or antagonism of opiate receptors on GH secretion in male and female rats. Life Sci 52:1443-50
Leidy Jr, J W; Romano, T M; Millard, W J (1993) Developmental and sex-related changes of the growth hormone axis in lean and obese Zucker rats. Neuroendocrinology 57:213-23
Gabriel, S M; Hunnicut, E H; Millard, W J et al. (1993) Influence of in vivo reproductive endocrine state on growth hormone-releasing factor stimulated adenylate cyclase activity in anterior pituitary fragments. Neuroendocrinology 57:63-9
Singh, M; Simpkins, J W; Layden, M P et al. (1992) Opiate modulation of growth hormone secretion is compromised during the steroid-induced luteinizing hormone surge. Neuroendocrinology 55:214-20
Peris, J; Coleman-Hardee, M; Millard, W J (1992) Cocaine in utero enhances the behavioral response to cocaine in adult rats. Pharmacol Biochem Behav 42:509-15
Badger, T M; Millard, W J; Owens, S M et al. (1991) Effects of gonadal steroids on clearance of growth hormone at steady state in the rat. Endocrinology 128:1065-72
Millard, W J; Romano, T M (1991) Comparison of efficacy of cysteamine in depleting prolactin immunoreactivity in different hyperprolactinemic animal models. Life Sci 49:1635-42
Simpkins, J W; Swager, D; Millard, W J (1991) Evaluation of the sites of opioid influence on anterior pituitary hormone secretion using a quaternary opiate antagonist. Neuroendocrinology 54:384-90
Cugini Jr, C D; Millard, W J; Leidy Jr, J W (1991) Signal transduction systems in growth hormone-releasing hormone and somatostatin release from perifused rat hypothalamic fragments. Endocrinology 129:1355-62
Millard, W J; Romano, T M; Layden, M P et al. (1991) Growth hormone secretion in the obese male rat: modulation by the gonadal and thyroid axes. Growth Dev Aging 55:91-103

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