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Publication : Sex steroid-dependent and -independent action of hydroxysteroid (17beta) Dehydrogenase 2: evidence from transgenic female mice.

First Author  Shen Z Year  2009
Journal  Endocrinology Volume  150
Issue  11 Pages  4941-9
PubMed ID  19797119 Mgi Jnum  J:158235
Mgi Id  MGI:4438309 Doi  10.1210/en.2009-0670
Citation  Shen Z, et al. (2009) Sex steroid-dependent and -independent action of hydroxysteroid (17beta) Dehydrogenase 2: evidence from transgenic female mice. Endocrinology 150(11):4941-9
abstractText  We have recently generated transgenic (TG) mice overexpressing human hydroxysteroid (17beta) dehydrogenase 2 enzyme (HSD17B2TG mice) under the ubiquitous chicken beta-actin promoter. As shown in the present study, the HSD17B2TG female mice presented with slower gain of body weight as compared with the wild-type (WT) littermates and suffered from ovarian dysfunction and mammary gland hyperplasia associated with increased expression of multiple pregnancy-associated genes. The macroscopic phenotype observed in the mammary gland was likely to be dependent on the increased progesterone and prolactin secretion, and a normal histological appearance was observed in HSD17B2TG mammary gland transplanted into a WT host. However, a significant suppression of several known estrogen target genes in the HSD17B2TG mammary transplants in WT females was observed, suggesting that HSD17B2 modulates estrogen action in vivo. Interestingly, the growth retardation of HSD17B2TG females was not efficiently rescued in the bi-TG mice expressing both HSD17B2 and HSD17B1 enzymes, and the bi-TG mice presented with certain masculinized phenotypes, including lack of nipples and closed vagina, recently reported for HSD17B1TG females. The present data suggest that HSD17B2 expression affects both sex steroid-independent and steroid-dependent pathways.
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