The anterior pituitary (adenohypophysis) is of ectodermal origin and forms during embryological development as an upward invagination of pharyngeal epithelium (Rathke pouch). Gonadotropes are specialized cells of the anterior pituitary that synthesize and secrete LH and FSH. GnRH binds to the GnRH type I receptor, a seven transmembrane G- protein- coupled receptor on the plasma membrane of gonadotropes: this activates a number of intracellular signalling cascades that enhance gonadotropin synthesis and secretion.
Each gonadotropin consists of α and β subunits, which dimerize. The biological specificity of LH and FSH relates to their unique β- subunits (the 121- amino acid LHβ and the 117- amino acid FSHβ, respectively). The α- subunit is common to LH, FSH, human chorionic gonadotropin (hCG), and thyrotropin. Gonadotropins also undergo variable post- translational modification— glycosylation in particular— which alters both bioactivity and elimination half- life.
Even though both LH and FSH are produced in a common cell type in response to GnRH stimulation, circulating LH and FSH concentrations vary differentially throughout ovulatory cycles. Numerous mechanisms underlie differential release of LH and FSH throughout the cycle. For example, higher frequency GnRH pulses favour LH synthesis and secretion, while lower frequency GnRH pulses enhance FSH synthesis and secretion (Figure 1). In addition, inhibins and oestradiol selectively restrain FSH re lease during the mid- and late follicular phase and the luteal phase.
Fig1. Impact of GnRH pulse frequency on LH and FSH secretion in GnRH- deficient monkeys. These monkeys were gonadectomized (but sex steroid- replaced) and rendered GnRH deficient via radiofrequency ablation of the arcuate nucleus. Normal gonadotropin secretion is maintained when exogenous GnRH was administered in a pulsatile fashion every hour. Decreasing the frequency of GnRH pulse administration to once every 3 hours was followed by a decrease in circulating LH but an increase in circulating FSH concentrations. Adapted with permission from Wildt L, Hausler A, Marshall G, Hutchison JS, Plant TM, Belchetz PE, Knobil E. Frequency and amplitude of gonadotropin- releasing hormone stimulation and gonadotropin secretion in the rhesus monkey. Endocrinology 1981; 109:376– 85. Copyright © 1981 Oxford University Press (10)
