Cytosol and nuclear progesterone-receptor concentrations in the rabbit endometrium during early pseudopregnancy under different treatments with estradiol and progesterone

In an attempt to understand the mechanism of the antiprogestational action of estrogens during early pseudopregnancy we determined the cytosolic and nuclear concentrations of progesterone receptors in the endometrium of rabbits treated with hCG followed by various combinations of estradiol and progesterone. The progestational response of the endometrium was followed by quantitation of the uteroglobin content in the uterine lumen.In rabbits treated with hCG alone there was a clear progestational response (40% relative uteroglobin content), but only 16% of the progesterone receptors were located in the nucleus.After additional treatment with progesterone the progestational response remained high (45% relative uteroglobin content), the total cellular content of progesterone receptor increased, and 5% of the complexes were found in the nucleus. These findings suggest that a consumption of nuclear progesterone receptor is required for progestational action.Treatment of pseudopregnant rabbits with estradiol resulted in a marked increase not only of the total cellular progesterone receptor but also of the percentage of it located in the nucleus (35%). Concomitantly, the progestational response was markedly inhibited (5% relative uteroglobin content). These results confirm the relevance of nuclear consumption of progesterone receptor for progestational action, and suggest that some antiprogestational effects of estrogens may be due to their interference with the mechanism of progesterone receptor processing.     

Management of multiple conceptions after gonadotropin-releasing hormone analog/human menopausal gonadotropin/human chorionic gonadotropin therapy

The treatment course of a 31-year-old infertility patient due to PCO disease is presented. Because the patient failed to conceive after various treatment cycles with CC, she was subjected to a combined GnRHa/hMG/hCG therapy. After plasma E2 levels had reached 2400 pg/ml, three leading follicles, with diameters of 20 to 24 mm, were detected. Induction of ovulation was achieved by 10,000 IU hCG. The patient conceived and developed ovarian hyperstimulation. At 8 weeks of gestation, seven cystic structures were detected within the uterine cavity, five containing single embryos, and two with twin embryos. All nine embryos were vital, as evidenced by their heart beats. Embryo reduction was achieved by transabdominal puncture on three occasions. The three surviving fetuses were carried to the 34th week of gestation. After delivery by cesarean section, three healthy babies developed normally. This communication illustrates the complications that can be associated with ovulation induction in PCO disease: ovarian hyperstimulation, polyovulation, multiple conceptions, and their clinical management.     

Die Kurzzeitwirkung von Clomiphencitrat (CC) auf die hypophysäre Gonadotropinausschüttung

Ohne Zusammenfassung     

Oestradiol production by luteinized human granulosa cells: evidence of the stimulatory action of recombinant human follicle stimulating hormone

In this study the effect of recombinant human follicle stimulating hormone (rFSH) on oestradiol production by human granulosa-lutein cells was examined in long-term culture, in the presence or absence of androgens. Cells were harvested at the time of follicular aspiration after ovarian hyperstimulation for in-vitro fertilization and cultured for 9 days. Granulosa cells were capable of secreting oestradiol spontaneously even without androgen and gonadotrophin support. Basal oestradiol secretion was relatively high and variable (421.3 +/- 159.3 pg/ml, mean +/- SEM, n = 13) on the first day and decreased gradually to 16.7 +/- 3.1 pg/ml on day 9. Addition of androgens (testosterone or androstenedione) to the incubation medium enhanced dose-dependently basal oestrogen production on days 5, 7 and 9. The androgen/oestrogen conversion rate remained constantly high during the culture, even without rFSH. After pre-incubation for 3 days, addition of rFSH resulted in a dose- and time-dependent increase in granulosa-lutein cell oestrogen production in the absence of exogenous androgens. Testosterone supplementation caused considerably higher basal oestradiol concentrations, however rFSH failed to further stimulate the oestrogen release from granulosa-lutein cells, suggesting that these cells cultured in vitro possess high aromatase activity even without rFSH support.      

Selektive Progesteronrezeptormodulatoren

Mifepristone has a strong antigestagenic effect, particularly in the uterus, and is currently used in clinical practice as an abortive agent. Asoprisnil is currently undergoing clinical trials as a selective progesterone receptor modulator. This substance has antigestagenic properties by blocking the gestagen-induced growth of leiomyomas. Gestagens inhibit apoptosis in mammary gland epithelia. This effect is reversed by antigestagens.     

Elevated serum progesterone concentrations during the early follicular phase of the menstrual cycle: clinical significance and therapeutic implications.

This study describes the incidence and clinical significance of hyperprogesteronemia in the early follicular phase of the menstrual cycle and the effects of prednisolone treatment in patients with this condition. Progesterone, testosterone and dehydroepiandrosterone sulfate (DHEAS) serum concentrations were determined in 316 consecutive patients admitted for infertility treatment. Elevated concentrations of progesterone in the early follicular phase could be detected in 36 cases (11.4%). In these patients, elevated testosterone and DHEAS concentrations could be detected in eight and ten cases, respectively. Serum concentrations of 17 alpha-hydroxyprogesterone and cortisol were normal in all patients. Treatment with 2.5-7.5 mg prednisolone/day normalized progesterone serum concentrations within 4-8 weeks. Twenty-four patients achieved a pregnancy either by timed intercourse or by intrauterine insemination (IUI) over the following 12 months.