Although the focus of significant investigative interest, the mechanisms involved in basal and gonadotropin-releasing hormone (GnRH)-stimulated luteinizing hormone (LH) release remain to be elucidated. Cyclic AMP has been proposed as an intermediary in signaling the release of LH. There is general agreement, however, that this nucleotide most likely does not elicit the immediate release of LH as is the case with growth hormone and prolactin; rather, the role of cyclic AMP may be to regulate the amount of LH available for release which is, in turn, a function of the prevailing neural and gonadal hormonal milieu. The mechanisms controlling cyclic AMP formation within the gonadotrope as well as those through which the nucleotide exerts its effects, and the question of whether all or only some gonadotropes synthesize and respond to cyclic AMP require definition. Thus, using rat anterior pituitary tissue maintained in several culture systems, a variety of probes which increase intracellular cyclic AMP, and a number of biochemical techniques, I propose to determine: I. Time/concentration relationships for GnRH-stimulated cyclic AMP accumulation. To be addressed specifically are the effects of gender and the hormonal environment of the donor animal on basal and GnRH-stimulated cyclic AMP accumulation. II. The effects of agents which increase intracellular cyclic AMP on cellular and released LH both basally and in response to GnRH. The physico-chemical and biological properties of LH basally and in response to cyclic AMP will be determined by isoelectric focusing and bioassay. In addition, glucosamine incorporation into LH and synthesis of LH will be monitored, the latter via determination of leucine incorporation and measurement of LH messenger RNA. The effects of the gonadal milieu on these processes will be closely scrutinized. III. The effects of agents which enhance intracellular cyclic AMP on basal and GnRH-stimulated LH release by individual gonadotropes. Using the hemolytic plaque assay, the question of whether all or only some cells demonstrate potentiation of LH release after stimulation of cyclic AMP production will be determined as will the effect of gender and the hormonal milieu on the numbers of """"""""responsive"""""""" versus """"""""non-responsive"""""""" cells.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD019170-01A1
Application #
3316384
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1985-04-01
Project End
1988-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Virginia
Department
Type
Schools of Medicine
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
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Krieg Jr, R J; Batson, J M; Martha Jr, P M et al. (1990) Gonadotropin-releasing hormone-stimulated luteinizing hormone secretion by perifused pituitary cells from normal, gonadectomized, and testicular feminized rats. Endocrinology 126:3022-7
Martha Jr, P M; Krieg Jr, R J; Batson, J M et al. (1989) Growth hormone secretion by individual somatotropes of the testicular feminized rat. Endocrinology 124:1124-30
Batson, J M; Krieg Jr, R J; Martha Jr, P M et al. (1989) Growth hormone (GH) response to GH-releasing hormone by perifused pituitary cells from male, female, and testicular feminized rats. Endocrinology 124:444-8
Pryor, J L; Krieg Jr, R J; Evans, W S et al. (1989) Luteinizing hormone secretion by male rat pituitary cells perifused in vitro: effect of experimental left varicocele and orchiectomy. J Androl 10:372-7
Veldhuis, J D; Christiansen, E; Evans, W S et al. (1988) Physiological profiles of episodic progesterone release during the midluteal phase of the human menstrual cycle: analysis of circadian and ultradian rhythms, discrete pulse properties, and correlations with simultaneous luteinizing hormone release. J Clin Endocrinol Metab 66:414-21
Sortino, M A; Evans, W S; Speciale, C et al. (1988) Gonadotropin-releasing hormone-stimulated phosphoinositide hydrolysis in the anterior pituitary. Modulation by protein kinase C but not by cyclic nucleotides. Neuroendocrinology 48:544-50
Krieg Jr, R J; Thorner, M O; Evans, W S (1986) Sex differences in beta-adrenergic stimulation of growth hormone secretion in vitro. Endocrinology 119:1339-42
Zmeili, S M; Papavasiliou, S S; Thorner, M O et al. (1986) Alpha and luteinizing hormone beta subunit messenger ribonucleic acids during the rat estrous cycle. Endocrinology 119:1867-9