Glucocorticoid repression of the reproductive axis: effects on GnRH and gonadotropin subunit mRNA levels.
Activation of the stress axis by glucocorticoids suppresses reproductive function in many species. Here, we performed studies to determine whether these effects are mediated at the level of the hypothalamus or pituitary or both, and to dissect the underlying molecular mechanisms, using two established rodent models. Rats were treated either chronically or acutely with glucocorticoids, and circulating gonadotropins, GnRH mRNA levels, and gonadotropin subunit mRNAs levels were measured. In model I, chronic treatment for 6 days with corticosterone (CORT) was used in adult intact male rats. CORT caused a significant decrease in serum LH but not FSH secretion compared to vehicle. Whereas pituitary LHbeta and FSHbeta mRNA levels were not affected by CORT treatment, hypothalamic GnRH mRNA was significantly decreased by 35-40%. In model II, acute blockade of the estradiol (E(2))-induced gonadotropin surge by dexamethasone (DEX) was used in 28-day-old female rats. DEX treatment resulted in substantially lower serum LH and FSH concentrations compared to vehicle, although DEX had no effect on GnRH mRNA and LHbeta mRNA levels. By contrast, FSHbeta mRNA levels were about 14-fold lower in DEX-treated females. Taken together, these results indicate that suppression of gonadotropin levels by chronic elevations in glucocorticoids/stress may be accounted for in part by suppression of GnRH mRNA levels, whereas short-term glucocorticoid treatment to block the gonadotropin surge appears to involve other mechanisms including decreased FSHbeta mRNA levels.
Gore
Andrea C
AC
Division of Pharmacology & Toxicology, College of Pharmacy, Institute for Neuroscience, The University of Texas at Austin, Austin, TX 78712, United States. andrea.gore@mail.utexas.edu
Attardi
Barbara
B
DeFranco
Donald B
DB
D000818:Animals; D003345:Corticosterone / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000235:genetics / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D006062:Gonadotropins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000502:physiology; D007986:Luteinizing Hormone / Q000235:genetics / Q000378:metabolism; D008297:Male; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects / Q000502:physiology; D013315:Stress, Psychological
D005938:Glucocorticoids; D006062:Gonadotropins; D021122:Protein Subunits; D012333:RNA, Messenger; D007987:Gonadotropin-Releasing Hormone; D003907:Dexamethasone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D003345:Corticosterone