SAT-151 - 切除术和性激素对垂体催乳素表达和调节的影响

Abstract:

Prolactin (PRL) is a pivotal hormone in female reproductive physiology, regulating ovarian function, luteal activity, and mammary gland development. Despite its importance, the specific roles of sex steroids in maintaining pituitary PRL synthesis remain incompletely understood. Ovariectomy (OVX) models provide a tool to examine the effects of sex steroid depletion on reproductive hormones, yet the relative contributions of estradiol (E2), progesterone (P4), and androgens such as dihydrotestosterone (DHT) to PRL regulation have not been fully clarified.

In this study, we investigated the effects of OVX and sex-steroid replacement on PRL expression in vivo, and the direct actions of E2, P4, and DHT on lactotroph-derived GH3 cells in vitro. Female Wistar rats underwent OVX or sham surgery, followed by supplementation with E2, P4, or DHT. Pituitary PRL expression, circulating PRL levels, and key hypothalamic regulators, including thyrotropin-releasing hormone (TRH) and dopamine pathway components, were quantified. In parallel, GH3 cells were used to examine direct steroid effects on PRL mRNA expression and promoter activity, as well as potential involvement of the locally expressed modulator follistatin (FST).

OVX markedly reduced pituitary and circulating PRL levels. E2 supplementation fully restored PRL expression, whereas P4 and DHT had no effect, both in OVX and ovary-intact animals. In GH3 cells, E2 directly enhanced PRL mRNA expression without increasing promoter-driven transcription, whereas P4 and DHT showed no stimulatory effects. Expression of hypothalamic TRH, tyrosine hydroxylase, and pituitary TRH and dopamine receptors remained unchanged after OVX, indicating that classical hypothalamic regulators are not responsible for the observed PRL suppression. Although OVX increased pituitary FST expression, FST did not modulate basal or TRH-stimulated PRL synthesis.

These results demonstrate that E2 is the primary sex steroid maintaining PRL production, acting directly on pituitary lactotrophs via mechanisms independent of hypothalamic TRH and dopamine pathways, and not mediated by FST. Our findings clarify the distinct role of E2 in PRL regulation and suggest that sex steroid depletion, rather than changes in hypothalamic regulators, underlies the reduction in PRL observed after ovarian removal. This study provides mechanistic insight into hormone-dependent regulation of PRL, with potential implications for understanding reproductive aging, ovarian insufficiency, and therapeutic interventions targeting PRL-associated reproductive dysfunctions.

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