Hydroxysteroid (17 beta)-dehydrogenase 1-deficient female mice present with normal puberty onset but are severely subfertile due to a defect in luteinization and progesterone production

• Hydroxysteroid (17 beta)-dehydrogenase type 1 (HSD17B1) catalyzes the conversion of low active 17-ketosteroids, androstenedione (A-dione) and estrone (E1) to highly active 17-hydroxysteroids, testosterone (T) and E2, respectively. In this study, the importance of HSD17B1 in ovarian estrogen production was determined using Hsd17b1 knockout (HSD17B1KO) mice. In these mice, the ovarian HSD17B enzyme activity was markedly reduced, indicating a central role of HSD17B1 in ovarian physiology. The lack of Hsd17b activity resulted in increased ovarian E1: E2 and A-dione: T ratios, but we also observed reduced progesterone concentration in HSD17B1KO ovaries. Accordingly with the altered steroid production, altered expression of Star, Cyp11a1, Lhcgr, Hsd17b7, and especially Cyp17a1 was observed. The ovaries of HSD17B1KO mice presented with all stages of folliculogenesis, while the corpus luteums tructure was less defined and number reduced. Surprisingly, bundles of large granular cells of unknown origin appeared in the stroma of the KO ovaries. The HSD17B1KO mice presented with severe subfertility and failed to initiate pseudopregnancy. However, the HSD17B1KO females presented with normal estrous cycle defined by vaginal smears and normal puberty appearance. This study indicates that HSD17B1 is a key enzyme in ovarian steroidogenesis and has a novel function in initiation and stabilization of pregnancy.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

Nyckelord

ovary

estrogen

fertility

HSD17B enzymes

RAT 17-BETA-HYDROXYSTEROID-DEHYDROGENASE TYPE-1

FOLLICLE-STIMULATING-HORMONE

ESTROGEN-RECEPTORS ALPHA

GRANULOSA-CELLS

CHORIONIC-GONADOTROPIN

MESSENGER-RNA

BREAST-CANCER

SEX REVERSAL

ER-ALPHA

IN-VIVO

Biochemistry & Molecular Biology

Biology

Cell Biology

LEAN MP

1990

ENDOCRINOLOGY

V126

P1796

UTANEN M

1993

ENDOCRINOLOGY

V133

P2639

UTANEN M

1992

INTERNATIONAL JOURNAL OF CANCER

V50

P386

URNETDULGUEROV N

1987

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM

V65

P757

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