Neuroendocrine vs. Paracrine Control of Follicle-Stimulating Hormone

In spite of the pivotal role FSH plays in the regulation of gametogenesis, we are far from understanding the regulatory mechanisms involved in the control of its synthesis, secretion, and functions. Part of the problem relates to its molecular heterogeneity and the unavailability of assay methods capable of distinguishing the various isoforms of FSH. Recent work has confirmed the existence of two modes of FSH secretion, the basal and the episodic modes. The major portion of FSH secretion appears to be in the basal mode. The episodic mode appears to consist of both GnRH-associated and non-GnRH-associated pulses of FSH. The intracellular mechanisms by which differential release of LH and FSH are facilitated by GnRH are just beginning to be unraveled and may involve different second-messenger systems. Local pituitary regulators such as activins, inhibins, and follistatins are receiving considerable attention in recent years as a means by which differential release of LH and FSH can be facilitated by GnRH and other neuroendocrine factors. In parallel, the search for a selective FSH-releasing factor (FSH-RF) continues. Identification of variant forms of GnRH in recent years has opened up the possibility that one GnRH variant may be the long-sought-after FSH-RF. From a functional aspect, an understanding of how FSH heterogeneity is regulated is also important, as the different mixes of FSH isoforms have the ability to fine-tune the follicular recruitment and selection process. This review focuses on the recent advances made in the neuroendocrine and paracrine regulation of FSH synthesis/secretion/heterogeneity and pinpoints areas of gaps in our knowledge.