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Progesterone modulation of gonadotropin secretion by dispersed rat pituitary cells in culture. II. Intracellular metabolism and progestin receptors.

Abstract：

:Dispersed, estradiol (E2)-treated, rat pituitary cell cultures were used to examine the intracellular processing of progesterone (P) associated with its modulation of gonadotropin-releasing hormone (GnRH)-stimulated luteinizing hormone (LH) secretion. Enhancement and suppression of LH release was only observed with acute and chronic exposures to P or other naturally occurring and synthetic progestins avidly bound by pituitary progestin receptors; such responses were inhibited by cotreatment with the antiprogestin RU486 but not with the antiandrogen flutamide, illustrating the importance of the P + receptor interactions. However, cotreatment with a 100-fold molar excess of the 5 alpha-reductase inhibitor 17 beta-N,N-diethyl-carbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one (4-MA) had no effect on the expression of P's modulatory actions. Additional studies using different E2 pretreatments revealed that P enhanced LH release when progestin receptor levels were elevated. Moreover, the magnitude and duration of P's influences on LH release increased in cells with higher receptor levels. However, there were several instances in which progestin receptor level and P modulation of LH release did not correlate. In several instances E2-induced progestin receptor levels stabilized at a maximal level whereas P enhancement of LH secretion continued to increase in size and duration. These findings underscore the importance of progestin receptors for P-induced modulation of LH secretion and illustrate that 5 alpha-reduction and further metabolism of P is not obligatory for the expression of these responses. In addition, our data demonstrate that the important cellular mechanisms underlying E2 priming of gonadotroph responsiveness to P entail the induction of progestin receptor levels and other as yet unidentified cellular processes.

journal_name

Mol Cell Endocrinol

journal_title

Molecular and cellular endocrinology

authors

Krey LC,Kamel F,MacLusky NJ

doi

10.1016/0303-7207(90)90181-7

subject

Has Abstract

pub_date

1990-01-22 00:00:00

pages

95-103

issue

2-3

eissn

0303-7207

issn

1872-8057

pii

0303-7207(90)90181-7

journal_volume

pub_type

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Progesterone modulation of gonadotropin secretion by dispersed rat pituitary cells in culture. II. Intracellular metabolism and progestin receptors.