Progesterone modulation of gonadotropin secretion by dispersed rat pituitary cells in culture. IV. Follicle-stimulating hormone synthesis and release

Abstract

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.

Antiprogestins Suppress Basal and Activin-Stimulated Follicle-Stimulating Hormone Secretion in an Estrogen-Dependent Manner1

“…Based on this evidence, we considered the possibility that the in vitro suppression of FSH secretion by the antiprogestins may have been due to agonist-like effects of the drugs. That this was not the case was clearly indicated by the finding that P 4 induced potent, concentration-dependent stimulation of FSH secretion, enhanced by priming with E 2 , in agreement with earlier reports by Drouin and Labrie (29) and Krey and co-workers (20). Both antiprogestins added at a low concentration antagonized this action of P 4 independent of E 2 .…”

“…Previous work from our laboratory and others demonstrated that RU486 is capable of suppressing FSH secretion in in vitro systems after prior in vivo administration of the drug to the pituitary donor animals (19) or upon direct addition to primary anterior pituitary cell culture (20). It is likely, however, that because of accumulation of locally produced activin (21) in the static cultures used in the latter study as well as in the present work, basal FSH secretion may, in fact, represent secretion stimulated by the autocrine or paracrine actions of endogenous activin (6).…”

Mechanisms Controlling the Function and Life Span of the Corpus Luteum

“…High levels of progesterone also result in decreased expression of the genes encoding the ␤-subunits of both LH (42) and follicle-stimulating hormone (FSH) (42,87) and the common ␣-subunit of the gonadotropins (18,42,87). These effects of progesterone on secretion of gonadotropins appear to be dependent on the total endocrine environment because, in some instances, progesterone can facilitate surges of gonadotropins induced by estradiol (17,27,40,41,193).…”

Regulation of Follicle-Stimulating Hormone Secretion by the Interactions of Activin-A, Dexamethasone and Testosterone in Anterior Pituitary Cell Cultures of Male Rats

“…In rats, glucocorticoids and testosterone (T) increase FSH secretion and FSHβ mRNA levels by yet uncharacterized mechanisms [20, 21, 22, 23, 24]. These effects are GnRH independent, indicating a direct action of glucocorticoids and testosterone at the pituitary level that leads to selective upregulation of FSHβ mRNA [20, 25]. The transcriptional effects of glucocorticoids and gonadal steroids involve ligand binding to nuclear receptors and translocation of the complex to the nucleus [26].…”