Androgens Exert Selective Effects on Protein Kinase C Induced LH and FSH Release in Rat Anterior Pituitary Cells in Culture

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Abstract
This study compares the selective effect of androgens on luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release induced either by LH-releasing hormone (LH-RH) or by protein kinase C activation in rat anterior pituitary cells in culture. In control cells, phorbol-12-myristate-13-acetate (PMA) stimulated the release of radioimmunoassayable LH and FSH in a dose-dependent manner at an ED50 value of 5.95 ± 1.45 nM. The maximal release of gonadotropins induced during a 3-hour incubation with PMA was 40–60% of that induced by LH-RH. Preincubation of the cells for 2–4 days with 10 nM 5α-dihydrotestosterone (DHT) decreased by approximately 60% the subsequent release of LH induced by 100 nM LH-RH or by 500 nM PMA during a subsequent 3-hour incubation. The inhibitory effect of DHT was completely suppressed by coincubation with the antiandrogen hydroxyflutamide. DHT exerted a similar inhibitory effect on LH release induced by another stimulator of protein kinase C activity, namely 1-oleoyl-2-acetylglycerol. The potent inhibitory action of DHT on LH-RH- or PMA-induced LH release was exerted at an ED50 value of approximately 10 pM. Contrary to the effect on LH, the FSH response to LH-RH or to PMA was increased by preincubation with 2 nM DHT, the stimulatory effect of the androgen being completely antagonized by hydroxyflutamide. The present data show that the characteristics of the selective and differential action of androgens on LH and FSH release are identical following stimulation by LH-RH or by protein kinase C activation. Such data suggest that the direct feedback action of androgens in pituitary gonadotrophs is exerted at post-LH-RH receptor sites which may involve protein kinase C itself and/or biochemical events induced by the enzyme.