The biology of gonadotroph regulation

Abstract

Purpose of review: To discuss recent progress in our understanding of pituitary gonadotroph development and gonadotropin gene regulation, with an emphasis on differential luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion and subunit synthesis, and the implications this may have on female reproductive health.

Recent findings: In the mature gonadotroph, there is an emerging concept that differential synthesis of gonadotropin beta-subunit genes, essential for cyclic reproductive function, is associated with modification of activation and/or stability of important regulatory proteins and transcription factors. Recent studies suggest that cellular events, which affect histone modification, play an essential role in both gonadotroph development and the ontogeny of gonadotropin subunit gene expression. Such dynamic events are under the orchestration of the hypothalamic neuropeptide gonadotropin-releasing hormone (GnRH), potentially through the ability of GnRH to activate several distinct signaling cascades within the gonadotroph.

Summary: Greater insight into the cellular events that are key to gonadotroph physiology will contribute to our understanding of abnormal gonadotropin secretion in disorders such as hypothalamic amenorrhea and polycystic ovarian syndrome (PCOS), and provide a context for the design of novel therapeutic approaches.

Figure 1

The potential role of MKPs in mediating the differential activation of MAPK components such as ERK1/2 in response to different GnRH pulse frequencies

Figure 2

Low and high GnRH pulse frequencies differentially alter gonadotropin β-subunit transcription through recruitment of histone acetyl transferases (HATs) and induction or modification of transcription factors