Dexamethasone alters responses of pituitary gonadotropin-releasing hormone (GnRH) receptors, gonadotropin subunit messenger ribonucleic acids, and gonadotropins to pulsatile GnRH in male rats.
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.
Rosen
H
H
Department of Internal Medicine, Veterans Administration Medical Center, Ann Arbor, Michigan 48105.
Dalkin
A
A
Haisenleder
D
D
Friberg
R D
RD
Ortolano
G
G
Barkan
A
A
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*
D006062:Gonadotropins; D012333:RNA, Messenger; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D003907:Dexamethasone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D004247:DNA