Gonadotrophin-releasing hormone modulation of gonadotrophins in the ewe: evidence for differential effects on gene expression and hormone secretion.
While the regulation of gonadotrophin secretion by gonadotrophin-releasing hormone (GnRH) has been well documented in both rats and sheep, its role in the synthesis of gonadotrophin subunits remains unclear. We have investigated the effects of the specific inhibition of GnRH by a GnRH agonist on the expression of gonadotrophin subunit genes and the subsequent storage and release of both intact hormones and free alpha subunit. Treatment with GnRH agonist for 6 weeks abolished pulsatile LH secretion, reduced plasma concentrations of FSH and prevented GnRH-induced release of LH and FSH. This was associated with a reduction of pituitary LH-beta mRNA and FSH-beta mRNA levels (to 5 and 30% of luteal control values respectively), but not alpha mRNA which was significantly increased (75% above controls). While there was a small decrease in the pituitary content of FSH (30% of controls), there was a drastic reduction in LH pituitary content (3% of controls). In contrast to the observed rise in alpha mRNA, there was a decrease in free alpha subunit in both the pituitary and plasma (to 30 and 80% of control levels). These results suggest that, while GnRH positively regulates the expression of both gonadotrophin beta-subunit genes, it can, under certain circumstances, negatively regulate alpha-subunit gene expression. Despite the complete absence of LH and FSH in response to GnRH, there remained a basal level of beta-subunit gene expression and only a modest reduction (50%) in the plasma levels of both FSH and LH, suggesting that there is a basal secretory pathway.(ABSTRACT TRUNCATED AT 250 WORDS)
McNeilly
J R
JR
Institute of Animal Physiology and Genetics, Edinburgh Research Station, Roslin, Midlothian.
Brown
P
P
Clark
A J
AJ
McNeilly
A S
AS
D000818:Animals; D015152:Blotting, Northern; D002064:Buserelin / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000032:analysis / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D015292:Glycoprotein Hormones, alpha Subunit / Q000032:analysis / Q000235:genetics; D007987:Gonadotropin-Releasing Hormone / Q000502:physiology*; D007986:Luteinizing Hormone / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D010902:Pituitary Gland / Q000737:chemistry / Q000378:metabolism*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011863:Radioimmunoassay; D012756:Sheep; D014158:Transcription, Genetic
D015292:Glycoprotein Hormones, alpha Subunit; D012333:RNA, Messenger; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D002064:Buserelin