TY - JOUR
T1 - Sex-specific response of bone cells to gonadal steroids
T2 - modulation in perinatally androgenized females and in testicular feminized male rats
AU - Weisman, Yosef
AU - Cassorla, Fernando
AU - Malozowski, Saul
AU - Krieg, Richard J.
AU - Goldray, David
AU - Kaye, Alvin M.
AU - Sömjen, Dalia
N1 - Funding Information:
We thank Niva Jaccard for expert technical assistance, Professor F. Naftolin for critical reading of the manuscript and unpublished information on aromatization in human bone, and Rona Levin for efficient processing of this manuscript. This study was supported in part by grants to A.M.K. from the Belle and Irving E. Meller Center for the Biology of Aging, Rehovot, Israel, and to S.M. from the National Institutes of Health, Bethesda, Maryland. A.M.K. is the Joseph Moss Professor of Molecular Endocrinology at the Weizmann Institute of Science.
PY - 1993/3
Y1 - 1993/3
N2 - 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 μg/rat) or DHT (50 μg/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 μM) or E2 (1μM) 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. Estrogen injection into Tfm males resulted in as large an increase in the specific activity of CK as found after DHT injection. These results suggest that during development the receptor-mediated pathway of response to both androgens and estrogens exists in the bones of both sexes. However, the sex-specific response to sex steroid hormones by diaphyseal bone appears to depend on both prior and continuing exposure to the dominant sex steroid in each sex. (Steroids 58: 126-133, 1993).
AB - 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 μg/rat) or DHT (50 μg/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 μM) or E2 (1μM) 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. Estrogen injection into Tfm males resulted in as large an increase in the specific activity of CK as found after DHT injection. These results suggest that during development the receptor-mediated pathway of response to both androgens and estrogens exists in the bones of both sexes. However, the sex-specific response to sex steroid hormones by diaphyseal bone appears to depend on both prior and continuing exposure to the dominant sex steroid in each sex. (Steroids 58: 126-133, 1993).
KW - androgenized female rats
KW - calvaria cells
KW - diaphyseal bone
KW - dihydrotestosterone
KW - estradiol
KW - gonadal steroids
KW - sexual differentiation
KW - testicular feminized male rats
UR - http://www.scopus.com/inward/record.url?scp=0027407603&partnerID=8YFLogxK
U2 - 10.1016/0039-128X(93)90049-S
DO - 10.1016/0039-128X(93)90049-S
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AN - SCOPUS:0027407603
SN - 0039-128X
VL - 58
SP - 126
EP - 133
JO - Steroids
JF - Steroids
IS - 3
ER -