The vaginal epithelium of immature rats metabolizes androgens through an aromatase-like reaction: changes during the time of puberty.
Testosterone (T) at physiological levels can induce precocious vaginal opening without advancing the time of first ovulation. The present experiments were undertaken to test the hypothesis that the vaginal epithelium has the ability to aromatize androgens to estrogens. Using standardized conditions, we estimated aromatase activity using both 3H2O-release from [1 beta-3H]T and thin-layer chromatographic (TLC) characterization of estrogen formed after incubations with [1,2,6,7-3H] testosterone. Vaginal aromatase-like activity, as measured by the 3H2O-release assay, increased between the juvenile and peripubertal phases of development and remained elevated throughout puberty. In contrast, ovarian aromatase increased markedly during the early proestrus (EP) and late (first) proestrus (LP) phases of puberty but declined after the first ovulation. Vaginal aromatase-like activity was induced in vivo by either stimulation of ovarian steroidogenesis with pregnant mare's serum gonadotropin (PMSG), or by producing EP levels of serum T via testosterone-containing Silastic capsules. 4-Hydroxy androstenedione, a potent aromatase inhibitor, decreased both vaginal and ovarian aromatase activity in vitro in a concentration-dependent manner. Although the principal product of ovarian aromatase derived from [1,2,6,7-3H] T was identified as estradiol (E2), the identity of the vaginal estrogen product could not be firmly established. The vaginal metabolite comigrated with 16-keto-E2 in two TLC systems before and one TLC system after acetylation but failed to recrystallize as 16-keto-E2 diacetate and failed to co-elute with 16-keto-E2 diacetate on high performance liquid chromatography. This vaginal metabolite does not correspond to any of 13 steroids tested, including 2-hydroxy-E2, and it does not represent a 5 alpha-reduced metabolite of T.(ABSTRACT TRUNCATED AT 250 WORDS)
Lephart
E D
ED
Department of Physiology, University of Texas Southwestern Medical Center, Dallas 75235.
Mathews
D
D
Noble
J F
JF
Ojeda
S R
SR
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D000728:Androgens / Q000378:metabolism*; D000735:Androstenedione / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001141:Aromatase / Q000378:metabolism*; D047072:Aromatase Inhibitors; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004848:Epithelium / Q000378:metabolism; D004967:Estrogens / Q000096:biosynthesis; D005260:Female; D006064:Gonadotropins, Equine / Q000494:pharmacology; D010053:Ovary / Q000201:enzymology / Q000378:metabolism; D010060:Ovulation; D051381:Rats; D011919:Rats, Inbred Strains; D012741:Sexual Maturation; D013739:Testosterone / Q000378:metabolism; D014621:Vagina / Q000201:enzymology / Q000378:metabolism*; D014867:Water
D000728:Androgens; D047072:Aromatase Inhibitors; D004967:Estrogens; D006064:Gonadotropins, Equine; D014867:Water; D013739:Testosterone; D000735:Androstenedione; D001141:Aromatase; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C014594:formestane