17-Hydroxyprogesterone responses to gonadotrophin- releasing hormone agonist buserelin and adrenocorticotrophin in polycystic ovary syndrome: investigation of adrenal and ovarian cytochrome P450c17α dysregulation
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چکیده
to be elevated in .50% of patients with PCOS (Hoffman Departments of 1Obstetrics and Gynaecology and 2Endocrinology, et al., 1984). Using selective catheterization of the adrenal and Erciyes University, Faculty of Medicine, 38039 Kayseri, Turkey ovarian vessels, some hyperandrogenic women demonstrate 3To whom correspondence should be addressed significant adrenal androgen hypersecretion (Moltz et al., Abnormal regulation of cytochrome P450c17α causes the 1984). Approximately 40–60% of hyperandrogenic women exaggerated secretion of ovarian androgens in polycystic have excessive responses of adrenal androgens to adrenocortiovary syndrome (PCOS). This enzyme is active in both the cotrophic hormone (ACTH; Ehrmann et al., 1992; Barnes, ovaries and adrenal glands. We examined whether there is 1994). The mechanism responsible for the adrenal androgen an abnormal regulation of cytochrome P450c17α in the excess in women with PCOS is still an unresolved problem. adrenal gland by investigating the relationship of 17In patients with PCOS, studies conducted under basal condihydroxyprogesterone (17-OH progesterone) hyperresponstions and in response to a sustained ACTH stimulation revealed iveness to the gonadotrophin releasing hormone (GnRH) significantly higher concentrations of 17-hydroxyprogesterone agonist, buserelin, testing with 17-OH progesterone (17-OH progesterone) as compared to normal women (Lachelin response to adrenocorticotrophic hormone (ACTH) in et al., 1979). PCOS. In all, 68 women with PCOS and 24 normal Women with PCOS have a high 17-OH progesterone women were included in the study. Ultrasound, clinical and response to gonadotrophin releasing hormone (GnRH) agonist hormonal parameters were used to define PCOS. 17-OH testing with nafarelin (Barnes et al., 1989), buserelin (Şahin progesterone response to ACTH was measured in all and Keleştimur, 1993) or leuprorelin acetate (Suikkari et al., the women. In 52 of the 68 women with PCOS, 17-OH 1995). PCOS is thought to be caused by an increased activity progesterone response to buserelin was measured. The of steroidogenesis through 17-hydroxylation and/or increased mean basal 17-OH progesterone concentrations were simbut relatively inefficient activity of 17,20-lyase. Both ilar in both PCOS and control groups. PCOS women had 17-hydroxylase and 17,20-lyase activity arise from the action significantly higher net increment in 17-OH progesterone of the same enzyme, cytochrome P450c17α. This enzyme after ACTH administration (P<0.02). No significant correlabinds progesterone and converts it to 17-OH progesterone (by tions were found between the peak 17-OH progesterone 17α-hydroxylase activity) and 17-OH progesterone to androsvalues, the net increments in 17-OH progesterone and the tenedione (by 17,20-lyase activity) (Rosenfield et al., 1990). area under the 17-OH progesterone–response curves after Cytochrome P450c17α is important for ovarian and adrenal ACTH stimulation and buserelin test. Although 17-OH function. 17-OH progesterone is an essential precursor for progesterone response to ACTH was significantly higher cortisol. This enzyme is encoded by a single gene on chromoin the patients with PCOS than in the control subjects, the some 10 and is expressed in both the adrenal gland and in lack of relationship between 17-OH progesterone response ovarian theca cells (Miller, 1988; Takayama et al., 1996). to GnRH agonist buserelin and 17-OH progesterone This combined adrenal and ovarian expression of cytochrome response to ACTH stimulation suggests that the dysregulP450c17α hyperactivity may explain the well-known enhanced ation of the cytochrome P450c17α enzyme may not play a production of androgen by the adrenals in patients with PCOS. role in adrenal androgen excess seen in PCOS. Rosenfield et al. (1990) suggested that the abnormal regulation
منابع مشابه
Lack of relationship between 17-hydroxyprogesterone response to buserelin testing and hyperinsulinemia in polycystic ovary syndrome.
OBJECTIVE To determine whether hyperinsulinism affects cytochrome P450c17 alpha activity by investigating the correlation between 17-hydroxyprogesterone (17-OHP) hyper-responsiveness to the gonadotropin-releasing hormone (GnRH) agonist, buserelin, and the insulin response to oral glucose in polycystic ovary syndrome (PCOS). DESIGN Ultrasound, clinical and hormonal parameters were used to defi...
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