Human HSD17B1 expression masculinizes transgenic female mice.
When present in excess amounts during fetal life, androgens can impair female development by inducing masculinization. On way to modify fetal steroid concentration is by altering the expression of hydroxysteroid (17beta) dehydrogenases (HSD17Bs). Human HSD17B1 converts weak estrogen estrone to estradiol, and with lower catalytic efficiency, weak androgen androstenedione to testosterone. We have recently shown that over-expression of human HSD17B1 in transgenic mice results in masculinized phenotype in female mice. In the present study, we further show that in addition to the Müllerian ducts, HSD17B1TG females have internal structures resembling Wolffian ducts, and enlarged Skene paraurethral gland, also called the female prostate. HSD17B1 expression has been found in fetal human ovary, thus, it is possible that HSD17B1 contributes to maintain the normal steroid hormone concentration during development. Thereby, abnormal increase in the fetal expression of HSD17B1 could contribute to the development of hormonal imbalances, and so result in female masculinization.
Saloniemi
Taija
T
Department of Physiology, Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, FI-20014 Turku, Finland. taija.saloniemi@utu.fi
Welsh
Michelle
M
Lamminen
Tarja
T
Saunders
Philippa
P
Mäkelä
Sari
S
Streng
Tomi
T
Poutanen
Matti
M
D000818:Animals; D004960:Estradiol Dehydrogenases / Q000378:metabolism*; D005260:Female; D006801:Humans; D006984:Hypertrophy; D051379:Mice; D008822:Mice, Transgenic; D014770:Virilism / Q000201:enzymology*; D014928:Wolffian Ducts / Q000473:pathology
D004960:Estradiol Dehydrogenases; C513331:HSD17B1 protein, human