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Regulation of Lutenizing Hormone Secretion and Subunit Messenger Ribonucleic Acid Expression by Gonadal Steroids in Perifused Pituitary Cells from Male Monkeys and Rats¹

Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213

Address all correspondence and requests for reprints to: Dr. Stephen J. Winters, Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Montefiore N919, 200 Lothrop Street, Pittsburgh, Pennsylvania 15213. E-mail: winters{at}med1.dept-med.pitt.edu

The mechanisms by which gonadal steroids regulate gonadotropin secretion remain incompletely understood. As previous studies suggest that the pituitary actions of testosterone (T) and estradiol (E) differ in male primates and rodents, we compared the effects of 10 nM T, 0.1 nM E, and 10 nM dihydrotestosterone (DHT) on the LH response to hourly pulses of GnRH as well as the GnRH receptor (GnRH-R) and LH subunit messenger RNA (mRNA) levels in dispersed pituitary cells from intact male monkeys and rats. T suppressed (P < 0.01) and E increased (P < 0.05) GnRH-stimulated LH secretion by rat pituitary cells. With monkey pituitary cells, on the other hand, there was no significant effect of either T or DHT on GnRH-stimulated LH secretion. In E-treated monkey cells, a period of initial enhancement (P < 0.05) was followed by significant suppression (P < 0.05) of LH secretion. GnRH-R mRNA was unchanged by T or E in either rat or monkey cells. T suppressed LHß (P < 0.01) and -subunit (P < 0.01) mRNAs, whereas E increased -subunit (P < 0.01), but did not alter LHß mRNA levels in rat cells. In monkey cells, however, neither T nor E affected LHß or -subunit mRNA levels significantly. Our results identify different regulatory mechanisms by which testicular steroid hormones control LH secretion by the pituitary in male primates and rodents. We propose that the primary site of androgen negative feedback in the male primate is to restrain GnRH pulsatile secretion, whereas in the male rat T also decreases gonadotropin synthesis and secretion by directly affecting the pituitary. E suppresses GnRH-stimulated LH secretion in the primate pituitary, but amplifies the action of GnRH in the rat. Our data also reveal that the action of T to suppress LH secretion and subunit mRNA in male rats is not through decreased GnRH-R gene expression.

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