Circulating Immunoreactive Oxytocin During the Human Menstrual Cycle Comes From the Pituitary and Is Estradiol Dependent*

Abstract

The aims of this study were to 1) evaluate the relative contributions of hypothalamic and ovarian oxytocin (OT) to peripheral serum concentrations and 2) determine the relationship between serum OT and ovarian steroid concentrations. Four groups of women were studied: 1) women with spontaneous cycles (n = 4) and normal serum estradiol (E2), progesterone, LH, and FSH levels; 2) in vitro fertilization (IVF) patients (n = 8) undergoing ovarian hyperstimulation; 3) agonadal oocyte-recipient patients (n = 6) receiving replacement E2 and P therapy; and 4) postmenopausal women (n = 21). Peripheral serum samples were collected daily during a menstrual cycle from the normal and agonadal women and for 6 days before ovulation in the IVF group. Serum immunoreactive OT was measured by specific RIA after Sep-Pak extraction; the assay sensitivity was 0.6 pmol/L. Serum OT in the women with normal cycles increased during the follicular phase, reaching a peak 1 day after the LH surge, and decreased in the luteal phase [days 7, 16, and 21, 10.7 +/- 3.5 (mean +/- SE), 25.7 +/- 5.7, and 13.2 +/- 2.5 pmol/L, respectively; P less than 0.05]. Serum OT levels were higher in IVF patients before ovulation than in women with spontaneous cycles, but lower than those in the agonadal women, who had a peak value (49.1 +/- 9.6 pmol/L; P less than 0.05) on day 13 of E2/progesterone replacement therapy. Serum OT was positively correlated (r = 0.68, normal women; r = 0.91, oocyte recipients) with serum E2 values during the first part of the cycle (P less than 0.01). A similar positive correlation between serum OT and E2 was found in the postmenopausal women (r = 0.83). We conclude that serum OT before and around the time of ovulation comes mainly from the pituitary, and not from the ovary, and is E2 dependent.

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