Distribution and metabolism of 20 alpha-hydroxylated progestins in the female rat.
The C21 steroids, progesterone and 20 alpha-hydroxy-4-pregnen-3-one (20 alpha-DHP) play pivotal roles in the initiation, timing and maintenance of ovulatory function and pregnancy in female mammals. They also have growth factor and central nervous system (CNS) effects; some of these are non-genomic effects mediated through 5 alpha-reduced and 3 alpha-hydroxylated derivatives. These studies examined the in vivo uptake and conversion of 20 alpha-DHP in selected CNS sites and peripheral tissues after injection of [(3)H]-20 alpha-DHP. The effects of steroid mass, time after injection, and ovariectomy, adrenalectomy and estradiol treatment were assessed in the pineal gland, preoptic area of the hypothalamus (POA), medial basal hypothalamus (MBH), midbrain, cerebellum, cerebral cortex, anterior pituitary (AP), uterus and skeletal muscle. Tissue extracts were analyzed by scintillation counting and chromatography to quantify and localize 20 alpha-DHP and its 5 alpha-reduced derivatives. Injection of increasing mass of [(3)H]-20 alpha-DHP to ovariectomized/adrenalectomized (ovx/adx) rats results in a linear increase in (3)H-steroid 10 min post injection in all tissues. (3)H-steroid content increases with time over 1 h post injection in the pineal, AP and uterus. Tissue differences in (3)H-steroid level are observed with higher levels in pineal, MBH, POA, AP and midbrain than in cerebral cortex and cerebellum, and in uterus, ovary and adrenal than in muscle. Ovariectomy, adrenalectomy and estradiol treatment affect (3)H-steroid levels in a tissue dependent manner, and the metabolites of 20 alpha-DHP in MBH and AP differ between groups. The findings demonstrate that target tissues, including areas of the CNS, are able to selectively take up and retain 20 alpha-DHP, and also support a physiological role for this progestin and its metabolites in modulation of CNS and reproductive functions.
Nowak
Felicia V
FV
Department of Biomedical Sciences and Program in Neuroscience, Ohio University, Athens, OH 45701, USA. nowak@ohiou.edu
D004092:20-alpha-Dihydroprogesterone / Q000378:metabolism* / Q000493:pharmacokinetics*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D008956:Models, Chemical; D010053:Ovary / Q000502:physiology; D011372:Progestins / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D014018:Tissue Distribution
D011372:Progestins; D004092:20-alpha-Dihydroprogesterone; D004958:Estradiol