Estradiol control of expression and levels of estradiol-binding proteins in the medial preoptic area, medial hypothalamus and pituitary.
The brains of mammals have at least three estradiol-binding proteins: estradiol receptor-alpha (ERalpha), ERbeta, and sex hormone-binding globulin (SHBG). In this study we compare the effects of estradiol treatment on the expression of mRNA for these three estradiol-binding proteins in two reproductively important brain areas, the medial preoptic area-anterior hypothalamus (MPOA-AH) and medial hypothalamus (MH) as well as in the hippocampus in ovariectomized rats, using the reverse transcriptase-polymerase chain reaction (RT-PCR). We also used surface-enhanced laser desorption ionization time of flight (SELDI-TOF) mass spectrometry (MS) to analyze the effects of estradiol in ovariectomized rats on SHBG levels in the MPOA-MH as well as the neurohypophysis. In vivo estradiol treatment in ovariectomized rats eliminated or significantly reduced expression of all three estradiol-binding proteins in both the MPOA-AH and MH. This change in ERalpha, ERbeta, and SHBG expression did not occur in the hippocampus. Both Northern blot and DNA sequence analysis confirmed the results of the RT-PCR for SHBG. SELDI-TOF MS analysis demonstrated that in vivo estradiol treatments resulted in dramatically decreased levels of SHBG in the hypothalamus and that a reduction in SHBG mRNA by estradiol treatment also resulted in a reduction in SHBG protein levels. Estradiol treatment also eliminated detectable SHBG from the neurohypophysis, suggesting that estradiol controls SHBG levels in this release site. That in vivo estradiol treatments had the same inhibitory effects on mRNA levels for SHBG and both ERs suggests similar translational control mechanisms for all three steroid-binding proteins in the brain. That estradiol treatments also reduced pituitary SHBG suggests that such treatment releases SHBG from the neurohypophysis.
Gao
Guang
G
Department of Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota, USA.
Herbert
Zsöfia
Z
Kong
Jing
J
Gabrielson
Nathan
N
Mautz
Alan
A
Wu
Dongming
D
Jirikowski
Gustav F
GF
Caldwell
Jack D
JD
D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D003720:Densitometry / Q000379:methods; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D007033:Hypothalamus, Middle / Q000187:drug effects* / Q000378:metabolism; D010052:Ovariectomy / Q000379:methods; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D011233:Precipitin Tests / Q000379:methods; D011301:Preoptic Area / Q000187:drug effects* / Q000378:metabolism; D040081:Protein Array Analysis / Q000379:methods; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011959:Receptors, Estradiol / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012738:Sex Hormone-Binding Globulin / Q000235:genetics* / Q000378:metabolism
D012333:RNA, Messenger; D011959:Receptors, Estradiol; D012738:Sex Hormone-Binding Globulin; D004958:Estradiol