The purpose of this project has been to examine the dynamics of hormone storage in pituitary gonadotropes. The renewal proposal will examine key factors that may influence storage patterns and GnRH receptivity in the gonadotrope population. Previous studies have shown that the stimulated gonadotrope population is mostly multihormonal and that monohormonal gonadotropes are found among the smallest cells. Our studies suggest that the gonadotrope population is fluid; perhaps the monohormonal gonadotropes are activated as needed during reproductive life. The renewal period will test this hypothesis in three phases. Phase 1 will focus on cycling female rats. A potent biotinylated analog of GnRH will be localized cytochemically on gonadotropes during key stages of the estrous cycle when changes in the number of GnRH receptors have been reported. Double, protein A gold stains for gonadotropins will then be used to confirm the identity of the GnRH target cells in order to learn if monohormonal gonadotropes are activated during early proestrus. Morphometric studies will show if changes in the number of GnRH receptors reflect changes in the number of sites bound per cell, or the number of cells bound, or both. Phase 2 will focus on the differential storage of LH and FSH in multihormonal and monohormonal gonadotropes. GnRH stimulation of multihormonal gonadotropes results in a shift in gonadotropin stores to the cell periphery coupled with a dissociation of LH and FSH storage pools. The proposed renewal will examine the effect of pulsatile exposure to GnRH with and without steroid pre-treatment. Monohormonal gonadotropes will be studied to learn if they can be stimulated by GnRH to produce the other hormone. Dual stains for gonadotropins and tubulin or calmodulin will be used to determine if changes in cytoskeletal elements accompany the mobilization of gonadotropin stores. Phase 3 of this renewal period will continue the studies of gonadectomy cells. Dual stains for biotinylated GnRH and gonadotropins will be used to examine the effect of steroids on GnRH binding, kinetics of internalization, and differential storage of gonadotropins. Techniques employed during this renewal period will include affinity cytochemistry, immunocytochemistry, radioimmunoassay (gonadotropins), electron microscopy, tissue culture, cell separation, and stereometry. The proposed renewal is designed to explore the fluidity of the gonadotrope population in order to learn more about the role of monohormonal cells and how the multihormonal cells mobilize their different storage pools to effect non-parallel release of LH and FSH.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD015472-07
Application #
3313115
Study Section
Reproductive Biology Study Section (REB)
Project Start
1981-05-01
Project End
1989-09-29
Budget Start
1987-12-01
Budget End
1989-09-29
Support Year
7
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Texas Medical Br Galveston
Department
Type
Schools of Medicine
DUNS #
041367053
City
Galveston
State
TX
Country
United States
Zip Code
77555
Childs, G V (2000) Growth hormone cells as co-gonadotropes: partners in the regulation of the reproductive system. Trends Endocrinol Metab 11:168-75
Childs, G V; Unabia, G; Miller, B T et al. (1999) Differential expression of gonadotropin and prolactin antigens by GHRH target cells from male and female rats. J Endocrinol 162:177-87
Childs, G V (1997) Cytochemical studies of multifunctional gonadotropes. Microsc Res Tech 39:114-30
Childs, G V; Miller, B T; Miller, W L (1997) Differential effects of inhibin on gonadotropin stores and gonadotropin-releasing hormone binding to pituitary cells from cycling female rats. Endocrinology 138:1577-84
Armstrong, J; Childs, G V (1997) Changes in expression of epidermal growth factor receptors by anterior pituitary cells during the estrous cycle: cyclic expression by gonadotropes. Endocrinology 138:1903-8
Armstrong, J; Childs, G V (1997) Differential expression of c-fos in vitro by all anterior pituitary cell types during the estrous cycle: enhanced expression by luteinizing hormone but not by follicle-stimulating hormone cells. J Histochem Cytochem 45:785-94
Ghosh, B R; Wu, J C; Strahl, B D et al. (1996) Inhibin and estradiol alter gonadotropes differentially in ovine pituitary cultures: changing gonadotrope numbers and calcium responses to gonadotropin-releasing hormone. Endocrinology 137:5144-54
Childs, G V (1995) Division of labor among gonadotropes. Vitam Horm 50:215-86
Childs, G V; Unabia, G; Miller, B T (1994) Cytochemical detection of gonadotropin-releasing hormone-binding sites on rat pituitary cells with luteinizing hormone, follicle-stimulating hormone, and growth hormone antigens during diestrous up-regulation. Endocrinology 134:1943-51
Childs, G V; Unabia, G; Rougeau, D (1994) Cells that express luteinizing hormone (LH) and follicle-stimulating hormone (FSH) beta-subunit messenger ribonucleic acids during the estrous cycle: the major contributors contain LH beta, FSH beta, and/or growth hormone. Endocrinology 134:990-7

Showing the most recent 10 out of 30 publications