Neuroendocrine, autocrine, and paracrine control of follicle-stimulating hormone secretion

Abstract

Follicle-stimulating hormone (FSH) is a glycoprotein hormone produced by gonadotropes in the anterior pituitary that plays a central role in controlling ovarian folliculogenesis and steroidogenesis in females. Moreover, recent studies strongly suggest that FSH exerts extragonadal actions, particularly regulating bone mass and adiposity. Despite its crucial role, the mechanisms regulating FSH secretion are not completely understood. It is evident that hypothalamic, ovarian, and pituitary factors are involved in the neuroendocrine, paracrine, and autocrine regulation of FSH production. Large animal models, such as the female sheep, represent valuable research models to investigate specific aspects of FSH secretory processes. This review: (i) summarizes the role of FSH controlling reproduction and other biological processes; (ii) discusses the hypothalamic, gonadal, and pituitary regulation of FSH secretion; (iii) considers the biological relevance of the different FSH isoforms; and (iv) summarizes the distinct patterns of FSH secretion under different physiological conditions.

Figure 1.

Schematic diagram of the hypothalamic, pituitary (local), and ovarian regulation of FSH secretion in female mammals. At the hypothalamic level, GnRH pulses are transported to the anterior pituitary by the hypothalamic-hypophyseal portal vasculature to stimulate FSH synthesis and secretion by gonadotrope cells. There is also evidence suggesting the existence of a hypothalamic FSH-releasing factor (FSH-RF). At the anterior pituitary level, a local loop involving activin, inhibin, and follistatin regulates FSH secretion in an autocrine/paracrine fashion. At the ovarian level, estradiol and inhibin are two key negative feedback regulators of FSH secretion. While the ovary also produces activin and follistatin, these hormones are not believed to play an endocrine role in controlling FSH secretion.

Figure 2.

Schematic summarizing the general changes in circulating levels of FSH regulators, FSH secretory patterns, and posttranslational modifications of FSH during pubertal progression, menstrual cycle, and perimenopause transition in women (reviewed in Cumming, 1990; Padmanabhan et al., 2002; Ulloa-Aguirre et al., 2003; and Yding Andersen, 2017). CL, corpus luteum; DF, dominant follicle.