Effects of testosterone, dihydrotestosterone, and 17beta-estradiol on human ovarian tissue survival in culture.
OBJECTIVE
To investigate the effects of T, dihydrotestosterone (DHT), and 17beta-estradiol on human ovarian stromal tissue survival in culture and to identify steroids capable of inhibiting cell death in vitro.


METHODS
Prospective study.


METHODS
Academic research setting.


METHODS
Thirty women, aged 18-38 years, undergoing gynecological operations for benign conditions and eight women, aged 27-36 years, undergoing IVF because of tubal obstruction or male factor infertility.


METHODS
Cultured tissue was exposed to T, DHT, 17beta-estradiol, or the anti-androgen casodex.


METHODS
Immunohistochemistry for androgen receptor (AR), Southern blot analysis of DNA fragmentation, histology, and in situ end labeling of apoptotic DNA.


RESULTS
Androgen receptors were detected in the ovarian stroma and granulosa cells of the primordial follicles, although they were more clearly seen in primary follicles and more advanced-stage follicles. Testosterone only marginally suppressed ovarian tissue apoptosis in vitro. DHT was more effective than T, whereas 17beta-estradiol had no notable effect on the viability of the tissue. The effects of androgens on the ovarian tissue may be mediated through ARs, since blocking the receptors with an AR antagonist reversed the suppressive effect of DHT.


CONCLUSIONS
DHT may be useful for enhancing human ovarian tissue survival in vitro.
Otala
Marjut
M
Program for Developmental and Reproductive Biology, Biomedicum Helsinki and University of Helsinki, Helsinki, Finland. marjut.otala@hus.fi
Mäkinen
Sirpa
S
Tuuri
Timo
T
Sjöberg
Jari
J
Pentikäinen
Virve
V
Matikainen
Tiina
T
Dunkel
Leo
L
D000328:Adult; D000726:Androgen Antagonists / Q000494:pharmacology; D059002:Androgen Receptor Antagonists; D000813:Anilides / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D046508:Culture Techniques; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009570:Nitriles; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D011446:Prospective Studies; D011944:Receptors, Androgen / Q000378:metabolism; D013739:Testosterone / Q000494:pharmacology*; D014022:Tissue Survival / Q000187:drug effects; D014105:Tosyl Compounds
D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D000813:Anilides; D009570:Nitriles; D011944:Receptors, Androgen; D014105:Tosyl Compounds; D013196:Dihydrotestosterone; D013739:Testosterone; D004958:Estradiol; C053541:bicalutamide