EXPRESSION AND SECRETION OF INHIBIN AND ACTIVIN IN NORMAL AND NEOPLASTIC UTERINE TISSUES - HIGH-LEVELS OF SERUM ACTIVIN A IN WOMEN WITH ENDOMETRIAL AND CERVICAL-CARCINOMA
F. Petraglia et al., EXPRESSION AND SECRETION OF INHIBIN AND ACTIVIN IN NORMAL AND NEOPLASTIC UTERINE TISSUES - HIGH-LEVELS OF SERUM ACTIVIN A IN WOMEN WITH ENDOMETRIAL AND CERVICAL-CARCINOMA, The Journal of clinical endocrinology and metabolism, 83(4), 1998, pp. 1194-1200
Inhibins and activins are growth factors belonging to the trans formin
g growth factor-beta) family and are known to influence cell prolifera
tion and differentiation. Because transforming growth factor-beta is i
nvolved in physiological and tumoral changes of uterine tissues. the p
resent study aimed to evaluate whether human normal and neoplastic end
ometrial and cervical epithelial cells express and secrete inhibin A,
inhibin B, and activin A. To test this hypothesis, different approache
s were used. Ey RT-PCR, the expression of specific messenger RNAs (mRN
As) for the inhibin alpha, activin beta A and beta B subunits, and act
ivin receptor type II and type IIB was investigated: 1) in primary cul
tures of endometrial (stroma and epithelium) or cervical (epithelium)
cells from healthy women; and 2) in specimens of endometrial or cervic
al carcinoma. To demonstrate a possible secretion of the proteins, dim
eric inhibin A, inhibin B, and activin A were measured in culture medi
um of normal epithelial or stromal endometrial cells and in uterine wa
shing fluid of healthy women or patients with endometrial adenocarcino
ma. Levels of the proteins were also measured in serum of women with e
ndometrial or cervical carcinoma. Cultured endometrial stromal or epit
helial cells and epithelial cervical cells expressed inhibin alpha, ac
tivin beta A and beta B, and activin receptor type II and type IIB mRN
As. The same finding was obtained in specimens of endometrial or cervi
cal carcinomas. Dimeric inhibin A, inhibin BI and activin A were measu
red in culture medium of both endometrial and cervical cells. In parti
cular, resulting activin A levels were significantly higher in epithel
ial than in stromal cultured endometrial cells (P < 0.01). Dimeric pro
teins were also detected in the washing fluid of the uterine cavities
of healthy women (controls) and with endometrial adenocarcinoma, in wh
ich higher activin A levels mere found (P < 0.01 us. controls). Women
with endometrial carcinoma showed serum activin A levels significantly
higher than healthy controls (P < 0.01), which significantly decrease
d after surgical removal of endometrial or cervical tumors (P < 0.01).
The present study, for the first time, showed that inhibin A, inhibin
B, and activin A, as well as activin receptors, are expressed in norm
al and neoplastic human uterine tissues. A secretion of activin A from
tumoral cells into systemic circulation is suggested by the observati
on that the high levels in serum of patients with endometrial or cervi
cal carcinoma decreased after the surgical removal of the tumor.