Gonadotropin-releasing hormone-induced stimulation and desensitization of free α-subunit secretion mirrors luteinizing hormone and follicle-stimulating hormone in perifused rat pituitary cells

Jeffrey Weiss*, Karen A. Duca, William F. Crowley

*Corresponding author for this work

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

A pulsatile pattern of hypothalamic GnRH stimulation is necessary for the maintenance of pituitary LH and FSH secretion, with continuous GnRH leading to a decrement in response. Although the physiological pattern of free a-subunit secretion closely mimics that of LH, several reports have indicated that free α-subunit is not desensitized by continuous GnRH stimulation. To explore the basis of this phenomenon, we have evaluated the responses of all three gonadotrope secretory products to carefully coordinated administrations of pulsatile and continuous GnRH in a dispersed rat pituitary perifusion system. Sensitivities (ED50) to GnRH fell within a narrow range for free α-subunit (11.5 nM), LH (12.9 nM), and FSH (17.3 nM), although a greater mass of LH than free a-subunit or FSH was released after each pulse of GnRH. The response to a standard GnRH pulse (10 nM) administered every 15, 30, or 120 min for 9 h was very stable, with no evidence of priming, summation, or loss of response. LH, FSH, and free α-subunit did, however, show significantly (P < 0.05) higher pulse amplitudes with longer interpulse intervals. In contrast to previous observations in vivo, the three gonadotrope secretory products showed parallel desensitization in response to continuous infusions of GnRH. This loss of response was significant (P < 0.05) after exposure to as little as 0.1 (FSH) to 0.5 nM (LH and a-subunit) GnRH for 2 h or to higher concentrations of GnRH (10 nM) for as little as 15 min (LH, FSH, and α-subunit). These concentrations and durations of GnRH stimulation are within the range of values measured in vivo.We conclude that 1) free α-subunit, LH, and FSH have similar concentration and frequency responses to pulsatile GnRH, although the absolute amount of hormone released is different for each secretory product; 2) the frequency of pulsatile GnRH stimulation can function as an independent determinant of secretion for each of the three products; and 3) in contrast to observations in vivo, free α-subunit, LH, and FSH secretion desensitize similarly after exposure to concentrations or durations of GnRH that may occur in vivo. These observations raise the possibility that desensitization plays a role in the physiological regulation of gonadotrope secretion.

Original languageEnglish (US)
Pages (from-to)2364-2371
Number of pages8
JournalEndocrinology
Volume127
Issue number5
DOIs
StatePublished - Jan 1 1990

ASJC Scopus subject areas

  • Endocrinology

Fingerprint Dive into the research topics of 'Gonadotropin-releasing hormone-induced stimulation and desensitization of free α-subunit secretion mirrors luteinizing hormone and follicle-stimulating hormone in perifused rat pituitary cells'. Together they form a unique fingerprint.

  • Cite this