Control of gonadotropin secretion by follicle-stimulating hormone-releasing factor, luteinizing hormone-releasing hormone, and leptin

Fractionation of hypothalamic extracts on a Sephadex G-25 column separates follicle-stimulating hormone-releasing, factor (FSHRF) from luteinizing hormone-releasing hormone (LHRH). The FSH-releasing, peak contained immunoreactive lamprey gonadotropin-releasing hormone (1GnRH) by radio immunoassay, and its activity was inactivated by an antiserum specific to IGnRH. The identity of 1GnRH-III with FSHRF is supported by studies with over 40 GnRH analogs that revealed that this is the sole analog with preferential FSH-releasing activity. Selective activity appears to require amino acids 5-8 of 1GnRH-III. Chicken GnRH-II has slight selective FSH-releasing activity. Using a specific 1GnRH-III antiserum, a population of 1GnRH-III neurons was visualized in the dorsal and ventral preoptic area with axons projecting to the median eminence in areas shown previously to control FSH secretion based on lesion and stimulation studies. Some 1GnRH-III neurons contained only this peptide, others also contained LHRH, and still others contained only LHRH. The differential pulsatile release of FSH and LH and their differential secretion at different times of the estrous cycle may be caused by differential secretion of FSHRF and LHRH. Both FSH and LHRH act by nitric oxide (NO) that generates cyclic C guanosine monophosphate. 1GnRH-III has very low affinity to the LHRH receptor. Biotinylated 1GnRH-III (10(-9) M) labels 80% of FSH gonadotropes and is not displaced by LHRH, providing evidence for the existence of an FSHRF receptor. Leptin has equal potency as LHRH to release gonadotropins by NO. 1GnRH-III specifically releases FSH, not only in rats but also in cows. (C) 2001 IMSS. Published by Elsevier Science Inc.