Low aromatase activity in microsomes from complete hydatidiform mole.
The complete hydatidiform mole (CHM) is characterized by the presence of aberrant placenta, with hyperplasia of cyto- and syncytiotrophoblasts and the absence of maternal genetic information. Steroidogenesis in this condition is, thus, of special interest. In this study we investigated the kinetic parameters of aromatase in microsomes from CHM compared with those in normal early placenta (NEP). The enzyme activity was determined by measuring the conversion of [3H] testosterone to [3H]estradiol plus [3H]estrone. The Km value for testosterone was 33 nmol/L in CHM and 17 nmol/L in NEP of similar gestational ages. Aminoglutethimide, a nonsteroidal inhibitor, decreased in a dose-dependent manner and with the same potency the aromatization of testosterone in both tissues (ID50, 2 vs. 1 mumol/L in CHM and NEP, respectively). These results suggest that the enzymes from the two sources are kinetically similar. However, the enzyme efficiency, expressed as the maximum velocity/Km ratio, was 17-fold lower in CHM than in NEP tissue (1.22/33 vs. 10.68/17 min/mg.mL). These findings suggest that in molar pregnancy the decreased capacity of trophoblast tissue for the formation of estrogen could increase the testosterone concentration inside the molar vesicle, which, in turn, as we previously reported, inhibits progesterone formation. All of these data could provide an explanation for the low circulating level of progesterone, which may directly or indirectly affect the spontaneous expulsion of this aberrant tissue in the second trimester of pregnancy.
Genti-Raimondi
S
S
Departamento de Bíoquimica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Cordoba, Argentina.
Alvarez
C I
CI
Patrito
L C
LC
Flury
A
A
D000032:Abortion, Therapeutic; D000616:Aminoglutethimide / Q000494:pharmacology; D001141:Aromatase / Q000378:metabolism*; D005260:Female; D006801:Humans; D006828:Hydatidiform Mole / Q000201:enzymology*; D007700:Kinetics; D008861:Microsomes / Q000201:enzymology*; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D012016:Reference Values; D013379:Substrate Specificity; D014594:Uterine Neoplasms / Q000201:enzymology*
D000616:Aminoglutethimide; D001141:Aromatase