Gonadal steroid hormone regulation of human and mouse follicle stimulating hormone beta-subunit gene expression in vivo.
Transgenic mice that express a 10-kilobase human FSH beta (hFSH beta) gene exclusively in pituitary gonadotropes were used to study the regulation of hFSH beta gene expression by gonadal steroids. For comparison, the mouse FSH beta (mFSH beta) gene was studied in parallel in nontransgenic sibling (normal) mice. The hFSH beta gene showed a sexually dimorphic expression pattern, identical to mFSH beta, in the mouse environment. Intact normal and transgenic male mice had elevated (P < 0.05) levels of serum [16 +/- 2 ng/ml (normal); 38 +/- 6 (transgenic)] and pituitary FSH content [2 +/- 0.3 micrograms/mg protein (normal); 36 +/- 6 (transgenic)] and FSH beta mRNA [1.47 +/- 0.10 arbitrary density units (normal); 1.00 +/- 0.23 (transgenic)] compared to the corresponding female mice ([< 2.0 ng/ml (normal and transgenic)] [0.1 +/- 0.01 microgram/mg protein (normal); 0.2 +/- 0.03 (transgenic)] [< 0.03 arbitrary density units (normal and transgenic)]). Serum FSH levels were increased (P < 0.05) 2 weeks after castration of normal (22 +/- 2 ng/ml) and transgenic males (135 +/- 19 ng/ml) and were suppressed (P < 0.05) by testosterone [7 +/- 0.8 ng/ml (normal); 12 +/- 2 (transgenic)] or estradiol [14 +/- 1 ng/ml (normal); 16 +/- 1 (transgenic)] replacement. The increased serum FSH levels were associated with an inverse drop (P < 0.05) in pituitary FSH content to 1 +/- 0.1 microgram/mg protein in normal and 16 +/- 2 in transgenic males. Testosterone replacement further suppressed (P < 0.05) pituitary FSH content in transgenic (3 +/- 0.5 micrograms/mg protein) but not normal (1 +/- 0.1) males.(ABSTRACT TRUNCATED AT 250 WORDS)
Kumar
T R
TR
Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences University, Portland 97201-3098.
Low
M J
MJ
D000595:Amino Acid Sequence; D000728:Androgens / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000032:analysis / Q000235:genetics; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000032:analysis / Q000097:blood / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D006801:Humans; D015151:Immunoblotting; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009919:Orchiectomy; D010052:Ovariectomy; D010902:Pituitary Gland / Q000737:chemistry; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011863:Radioimmunoassay; D017422:Sequence Analysis, DNA; D012727:Sex Characteristics; D013045:Species Specificity; D013739:Testosterone / Q000494:pharmacology*
D000728:Androgens; D012333:RNA, Messenger; D013196:Dihydrotestosterone; D013739:Testosterone; D004958:Estradiol; D005640:Follicle Stimulating Hormone; D004247:DNA