Sex-specific response of bone cells to gonadal steroids: modulation in perinatally androgenized females and in testicular feminized male rats.
We have found previously that rat diaphyseal bone in vivo, as well as rat embryo calvaria cells in culture, show a sex-specific response to gonadal steroids in stimulation of creatine kinase (CK)-specific activity, and the rate of [3H]thymidine incorporation into DNA; male-derived cells responded only to testosterone or to dihydrotestosterone (DHT), whereas female-derived cells were stimulated exclusively by estradiol (E2). In this study, we tested whether developmental hormone manipulation could alter this sex specificity. We showed that diaphyseal bone of prenatally or neonatally androgenized female rats responds to a single injection of either E2 (5 micrograms/rat) or DHT (50 micrograms/rat) at 3-4 weeks postandrogenization. This response of androgenized female diaphyseal bone to androgen gradually declines; 3 months posttreatment, diaphyseal bone no longer responds to DHT and reverts to its original sex specificity. Rat embryo calvaria cell cultures prepared from female fetuses androgenized in utero showed the same lack of hormonal specificity, that is, the cells responded to both E2 (30 nM) or DHT (300 nM). Cells derived from the male siblings of the prenatally androgenized rats were not affected and responded only to DHT. In contrast to experiments in utero, in vitro administration of testosterone (1 microM) or E2 (1 microM) to calvaria cells from female embryos failed to cause the cells to respond to DHT. Androgen receptor-deficient (Tfm) male rats, which have approximately 10% of the normal response to androgens, also showed a response to both testosterone and E2 in comparison to their normal male siblings, whose bones responded only to androgens.(ABSTRACT TRUNCATED AT 250 WORDS)
Weisman
Y
Y
Bone Disease Unit, Ichilov Hospital, Sackler Faculty of Medicine, Tel Aviv University, Israel.
Cassorla
F
F
Malozowski
S
S
Krieg
R J
RJ
Goldray
D
D
Kaye
A M
AM
Sömjen
D
D
D013734:Androgen-Insensitivity Syndrome / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001842:Bone and Bones / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D002478:Cells, Cultured; D003402:Creatine Kinase / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D013196:Dihydrotestosterone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012727:Sex Characteristics; D013739:Testosterone / Q000494:pharmacology*
D012739:Gonadal Steroid Hormones; D013196:Dihydrotestosterone; D013739:Testosterone; D004958:Estradiol; D004247:DNA; D003402:Creatine Kinase