Regulation of rat luteinizing hormone beta gene expression in transgenic mice by steroids and a gonadotropin-releasing hormone antagonist.
Transcriptional regulation of the rat LH beta (rLH beta) gene was studied through the use of transgenic mice bearing a region of the rLH beta gene (from -2 kb to +41 bp) linked to a luciferase (LUC) reporter gene. All 7 founder mice were successfully bred with B6SJLF1 mates and exhibited germ line transmission of the LH beta LUC transgene. Levels of rLH beta LUC activity were highest in the pituitary, but activity was also detected in ovary, testis, and hypothalamus. Pituitary rLH beta LUC activity was found to be regulated by gender, gonadectomy, gonadal steroid replacement, and GnRH antagonist administration. Females had higher basal pituitary rLH beta LUC activity than males. This activity was increased 2- to 4-fold seven days postovariectomy, and stimulated activity was suppressed to intact levels by daily injections of 17 beta estradiol (E2; 300 ng). In males, castration increased pituitary LUC activity 2- to 4-fold, and this suppressed to intact levels by daily injections of 25 micrograms dihydrotestosterone (DHT). The postgonadectomy rise in pituitary rLH beta LUC activity in females and males was blocked by daily administration of the GnRH antagonist Antide (60 micrograms), which also suppressed serum LH and LH beta mRNA levels to a similar extent. Rat LH beta LUC activity measured in the hypothalamus was not altered by gonadectomy or gonadal steroid or Antide treatment, demonstrating that this regulation is pituitary-specific. These results indicate that feedback regulation of pituitary rLH beta LUC gene expression is operational in this transgenic mouse model.(ABSTRACT TRUNCATED AT 250 WORDS)
Fallest
P C
PC
Department of Internal Medicine, University of Virginia, Charlottesville, USA.
Trader
G L
GL
Darrow
J M
JM
Shupnik
M A
MA
D000818:Animals; D015139:Blotting, Southern; D013196:Dihydrotestosterone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D007031:Hypothalamus / Q000378:metabolism; D008156:Luciferases / Q000235:genetics; D007986:Luteinizing Hormone / Q000235:genetics*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009842:Oligopeptides / Q000494:pharmacology; D009919:Orchiectomy; D009928:Organ Specificity; D010052:Ovariectomy; D010902:Pituitary Gland / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins; D013256:Steroids / Q000494:pharmacology*
D009842:Oligopeptides; D011993:Recombinant Fusion Proteins; D013256:Steroids; D013196:Dihydrotestosterone; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D007986:Luteinizing Hormone; C057022:iturelix; D008156:Luciferases