Estradiol-treated, rat pituitary cells were studied to examine the effects of progesterone (P) on follicle-stimulating hormone (FSH) synthesis and secretion. Progesterone was administered prior to or concurrent with 3 h secretory challenges with either gonadotropin-releasing hormone (GnRH), the iontophore A23187, the protein kinase C activator phorbol 12,13-myristate (PMA), or no secretagogue. Medium FSH levels and cell FSH stores were quantified by radioimmunoassay and bioassay. Acute (< 6 h) exposures to P increased medium levels of immunoreactive and bioactive FSH following GnRH challenge without influencing total (cell + medium) values whereas chronic (9-24 h) treatments increased both parameters. Chronic P elevated total FSH levels even when no secretagogue was present. Studies with antiprogestins, 5 alpha-dihydroprogesterone and 5 alpha-reductase inhibitors revealed that this direct action of P depended on progestin receptor occupation but not on 5 alpha-reduction. These studies indicate that P selectively increases bioactive and immunoactive FSH levels, presumably by increasing FSH synthesis, and characterize the time course and cellular mechanisms of this response. To accommodate for P modulation of total FSH levels, FSH secretion was standardized as the percentage of cellular stores available for release. Progesterone modulation of GnRH-stimulated FSH secretion was multiphasic, i.e. increased at 0-6 h, unchanged at 9 h and suppressed at 24 h. Acute and chronic exposures to P similarly modulated A23187-stimulated FSH release, whereas both P treatments increased PMA-stimulated FSH secretion. In these experiments P modulated luteinizing hormone secretion in parallel fashion, suggesting that common cellular mechanisms underlie peptidergic and steroidal regulation of the secretion of both gonadotropins.
