title: Dexamethasone alters responses of pituitary gonadotropin-releasing hormone (GnRH) receptors, gonadotropin subunit messenger ribonucleic acids, and gonadotropins to pulsatile GnRH in male rats.
abstract: Dexamethasone (Dex), when administered in high doses, has been shown to suppress spontaneous and GnRH-induced gonadotropin secretion, but the level and the mechanism(s) of this effect are unknown. We administered Dex to castrate testosterone-replaced male rats to determine if gonadotropin gene expression is affected and whether Dex differentially influences GnRH-modulated parameters of gonadotrope function: induction of GnRH receptors (GnRH-R) and gonadotropin synthesis and secretion. GnRH was given iv at 25 ng/pulse at 8, 30, and 120 min intervals for 48 h. Rapid GnRH injection frequency preferentially increased alpha and LH-beta messenger RNA (mRNA) responses to GnRH as well as LH secretion. Slower GnRH injection frequencies were required to increase levels of GnRH-R, FSH-beta mRNA, and FSH secretion. Dex selectively inhibited the serum LH, alpha, and LH-beta mRNA responses to GnRH, but not the serum FSH or FSH-beta mRNA responses. Additionally, it augmented the GnRH-induced increase in GnRH-R. We conclude: 1) induction of GnRH-R, gonadotropin synthesis, and secretion require different modes of GnRH stimulation; 2) Dex acts directly on the gonadotrope to differentially modulate GnRH-induced increases in GnRH-R levels, gonadotropin gene expression, and gonadotropin secretion; and 3) GnRH effects upon induction of GnRH-R, LH, and FSH synthesis and secretion are likely to be mediated via different cellular pathways.
authors.affiliation: Department of Internal Medicine, Veterans Administration Medical Center, Ann Arbor, Michigan 48105.
authors.forename: H
authors.initials: H
authors.lastname: Rosen
authors.forename: A
authors.initials: A
authors.lastname: Dalkin
authors.forename: D
authors.initials: D
authors.lastname: Haisenleder
authors.forename: R D
authors.initials: RD
authors.lastname: Friberg
authors.forename: G
authors.initials: G
authors.lastname: Ortolano
authors.forename: A
authors.initials: A
authors.lastname: Barkan
mesh_terms: D000818:Animals; D004247:DNA / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D006062:Gonadotropins / Q000235:genetics / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D010902:Pituitary Gland / Q000378:metabolism*; D011673:Pulsatile Flow; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011966:Receptors, LHRH / Q000378:metabolism*
chemical_list: D006062:Gonadotropins; D012333:RNA, Messenger; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D003907:Dexamethasone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D004247:DNA