Interaction between 16α,17α-cyclopropane progesterone and progesterone receptors in rat uterus

Binding of³H-16α, 17α-cyclopropanoprogesterone (CPG) and³H-progesterone (PG) to progesterone receptors in soluble fraction of rat uterus is studied. It is shown that CPG and PG specifically bind to the protein with similar affinity and binding capacity. Unlabeled PG competitively inhibits the binding of CPG, and unlabeled CPG competitively inhibits the binding of PF with the same efficiency. Dissociation of CPG- and PG-receptor complexes is characterized by the same dissociation constant. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 125, No. 5, pp. 532–534, May, 1998     

The effect of peritoneal macrophage-derived factor(s) on ovarian progesterone secretion and LH receptors: the role of calcium.

Macrophages and their secretory products, cytokines, play an integral role in many reproductive processes. In this study we examined the effect of conditioned media from cultured human peritoneal macrophages on progesterone production by granulosa cells and the role of calcium in this process. Macrophages were pretreated with various concentrations of a calcium channel blocker (verapamil) or a calcium ionophore (A23187). Macrophage-conditioned media (MCM) or cell-free media that contained calcium channel modifiers were added at three dose levels to cultured porcine granulosa cells. Progesterone production and LH receptor content were determined. Macrophage-conditioned media alone elevated basal progesterone production, but significantly attenuated granulosa cell LH receptor content. These effects were neither potentiated nor suppressed by pretreating macrophages with verapamil. However, production of the LH receptor lowering factor(s) appeared to be suppressed by calcium ionophore. We conclude that (1) one or more factors produced by macrophages have a net stimulatory effect on basal progesterone production and these factor(s) may not be calcium-dependent and (2) macrophage-derived secretory products reduce granulosa cell LH receptor content. The production of these factor(s) may be calcium-dependent.     

Angiomyofibroblastoma of the vulva: Case report with immunohistochemical, ultrastructural and DNA ploidy studies and a review of the literature

A case of anglomyofibroblastoma of the vulva in a 49-year-old woman was examined. The tumor measured 3×2.5×2 cm and appeared light gray to tan In color on the cut surface. Light microscopic examinations revealed that spindle or oval shaped tumor cells were arranged in loose edematous stroma with numerous thin-walled vessels. Ultrastructurally, cell organellae were not well developed but intracytoplasmic filaments of intermediate size were abundant in the tumor cells. Desmin, CD34 and vimentin immunoreactivity were detected in almost all of the tumor cells. Both estrogen and progesterone receptors were diffusely expressed In the tumor, suggestive of the sex sterold-dependency of this tumor. The Ki-67 labeling index was less than 1% and the DNA content of the tumor cells, which was examined by image cytometry, demonstrated diploidy (DNA index=0.97). These findings may reflect the quiescent or slow growing features of angiomyofibroblastoma.     

The effect of a levonorgestrel-releasing intrauterine device on human endometrial oestrogen and progesterone receptors after one year of use

Thirty-four women bearing a levonorgestrel-releasing intrauterine device, 20 micrograms/day (LNG-IUD-20), for 12-15 months were recruited. Endometrial biopsies were collected during the late proliferative phase of the cycle (on cycle days 10-12) before (control) and after the use of the IUD for 12 months, and assayed for oestrogen receptors (ER) and progesterone receptors (PR). An immunohistochemical technique with the peroxidase-antiperoxidase detection system (PAP method) was employed. D75 and JZB39 were the primary antibodies for ER and PR respectively. The immunostaining semiquantitative analysis was performed with a computerized microscope image processor, and expressed as 'grey value'. Both endometrial ER and PR populations were significantly lower after insertion of the IUD (P < 0.01) than in control biopsies. The intensity of nuclear staining and the percentage of positively stained cells for ER and PR in women with LNG-IUD were each about 50% of those in control biopsies. The results suggested that LNG released locally from the IUD has a depressive action on the ER and PR, which may contribute to the contraceptive effectiveness of this type of IUD and also to the possible causes of LNG-IUD-induced irregular bleeding and amenorrhoea.     

Effect of antenatal dexamethasone therapy on maternal plasma human chorionic gonadotrophin, oestradiol and progesterone

The aim of this study was to determine whether the current regimen of dexamethasone administration to induce fetal lung maturation affected the circulating concentrations of placental hormone. A standard regimen of dexamethasone that comprised two doses of 12-mg intramuscular injections, 12 h apart was administered to 12 pregnant women to promote fetal lung maturation in anticipation of premature delivery before 34 completed weeks of gestation. Blood samples were collected before starting the dexamethasone therapy, 24 h, and 48 h after completing therapy for the measurement of the plasma concentrations of human chorionic gonadotrophin (HCG), oestradiol and progesterone. There was a progressive fall in the plasma concentrations of HCG following dexamethasone therapy (P = 0.049 and P = 0.034, 24-h and 48-h post therapy respectively). There was an initial fall in the plasma concentrations of oestradiol after dexamethasone therapy (z = 3.059; P = 0.002, 24-h post therapy), which recovered by 48 h (P = 0.239). There was no difference between the plasma concentrations of progesterone at the three time points. The effect of dexamethasone on HCG concentrations suggests that it has a direct inhibitory effect on placental hormone synthesis or secretion. Further studies are needed to define the mechanism of action of dexamethasone on placental HCG production.     

Pregnancy and sex steroid hormones enhance circulating calcitonin gene-related peptide concentrations in rats

Calcitonin-gene-related peptide (CGRP) is a 37 amino acid neuropeptide synthesized primarily in dorsal root ganglia (DRG) and distributed widely in the perivascular nerves, suggesting that this peptide may play a role in the regulation of peripheral vascular tone. Since female sex steroid hormones have been implicated in the regulation of peripheral vascular tone during pregnancy, we postulated that they may alter the concentration of CGRP in the circulation and thus modulate the increased blood flow observed during pregnancy. In the present study, we measured changes in plasma concentrations of CGRP in non-pregnant, pregnant, and post-partum rats. Groups of ovariectomized rats were treated s.c. for 3 days either with 17beta-oestradiol (2.5 microg per injection twice daily), progesterone (2 mg per injection twice daily), or vehicle. Another group of adult, non-pregnant rats at dioestrus stage of the oestrous cycle was also used in this study. Plasma concentrations of CGRP were higher (P < 0.05) in rats on day 19 of pregnancy (22.0 +/- 3.0 pmol/l) compared to that during delivery (5. 0 +/- 2.0), post-partum day 2 (2.0 +/- 0.7) or in non-pregnant (4.9 +/- 1.6) state. Furthermore, in adult ovariectomized (6.0 +/- 0.6) rats, plasma CGRP concentrations were increased significantly (P < 0. 05) by oestradiol (10.0 +/- 1.0), progesterone (9.5 +/- 1.0) and oestradiol + progesterone (14.0 +/- 1.0). Thus, circulating concentrations of CGRP are elevated during pregnancy and by oestrogen and progesterone, suggesting that the elevated concentrations of CGRP may play an important role in vascular adaptations that occur during pregnancy.     

Intracerebral implantation of progesterone: re-examination of the brain sites responsible for facilitation of sexual receptivity in estrogen-primed ovariectomized rats.

Ovariectomized female rats were tested for sexual receptivity following SC priming with threshold doses of estradiol benzoate and intracerebral 27 ga implants of either progesterone or cholesterol. All females were repeatedly tested under both intracerebral hormone implant conditions. Cholesterol implants failed to activate receptivity, while progesterone implants in the interpeduncular-ventral tegmental area produced near maximal levels of receptivity within 30 min after implantation. Progesterone implants in the medial hypothalamus, anterior hypothalamus, preoptic area, pons, mesencephalic reticular formation and lateral mesencephalon failed to activate sexual receptivity.     

Oocyte and embryo quality as well as pregnancy rate in intracytoplasmic sperm injection are not affected by high follicular phase serum progesterone

The effect of elevated serum progesterone concentrations (>1ng/1) on or before the day of human chorionic gonadotrophin(HCG) injection on the outcome of women receiving gonadotrophin-releasinghormone analogue (GnRHa)/ human menopausal gonadotrophin (HMG)for ovarian stimulation prior to intracytoplasmic sperm injection(ICSI) was evaluated. A total of 1275 ICSI cycles were analysedretrospectively. In 53 cycles (4.5%), serum progesterone concentrationswere > 1 ng/ml. Patients in the high progesterone group hadsignificantly higher oestradiol and luteinizing hormone concentrationson the day of HCG injection. The characteristics of the cumulus-coronacell complexes and the nuclear maturity of the oocytes weresimilar in the groups of patients with high and low serum progesteronelevels. Fertilization and cleavage rates as well as embryo qualitywere not different in the two groups. No difference in implantationor clinical pregnancy rates was observed between the high progesteroneand low progesterone groups. Moreover, the cumulative exposureto progesterone during the follicular phase, as expressed bythe area under the curve (AUC), and the duration of exposureto high serum progesterone levels (>1 ng/ml) were not significantlydifferent between pregnant and non-pregnant women in the highprogesterone group. We conclude that in ICSI cycles pretreatedwith GnRHa, increased serum progesterone concentrations on orbefore the day of HCG injection do not affect ICSI outcome.     

Induction of ovulation in rabbits by pure urinary Iuteinizing hormone

In 18-week-old nulliparous rabbit dose, ovulation was inducedwith 50 IU of pure urinary luteinizing hormone (LH; LHgroup),or 50 IU of ohuman chorionic gonadotrophin (HCG; HCG group),in order to detemine the effect of these treatments on 17-oestradioland progesterone concentrations, and on oocyte and embryo quality.Luteinizing follicles, recovered oocytes, progesteronoe concentrationand grade 5 embryos were significantly reduced when pure urinaryLH was used. Statistically significant correlations were found:(i) between oestradiol concentration and number of degeneratedoocytes in both groups (positive); (ii) between oestradiol concentrationand grade 1 and 2 embrayos (negative), and grade 5 embryos (positive)in the HCG group; (iii) between progesteronoe concentrationand metaphase II oocytes(negatice), and between progesteroneand grade 5 sembryos (positive), in the HCG group; and (iv)between progesterone and oestradiol concentrations (negative)in the LH group. It seems that the oestrsdiol to progegsteroneratio improves during the early luteal phase when ovulationis induced with LH, and that oestradiol and progesterone concentrationscould play a role in dtermining oocyte and embryo quality     

The stimulatory effect of α‐melanotropin on progesterone release from rat granulosa cells is inhibited by interleukin‐1β and by tumour necrosis factor‐α

Aim: Several studies have shown that a variety of peptides and cytokines are involved in ovarian regulatory mechanisms; however, their exact function is still unclear. In this work we study whether the administration of peptide α‐melanotropin and the cytokines interleukin‐1β (IL‐1β) and tumour necrosis factor‐α (TNF‐α) on their own modify the release of progesterone in cultured granulosa cells (GC) from pro‐oestrous rats. We also investigate an interaction between these cytokines and α‐melanotropin in the modulation of progesterone secretion. Methods: Granulosa cells were collected from the ovaries of female Wistar rats and cultured for up to 24 h in the presence of different concentrations of α‐melanotropin, cytokines or a combination of both. Progesterone concentration was measured by radioimmunoassay. Results: The addition of α‐melanotropin in a dose of 0.01 and 0.1 mm had no effect on progesterone release, whereas a dose of 1 mm significantly increased progesterone release (P < 0.01) compared with the control culture. Progesterone release was not modified when different concentrations of interleukin‐1β or TNF‐α were added to the cell cultures. However, when interleukin‐1β or TNF‐α were added simultaneously with 1 μm α‐melanotropin, a significant reduction (P < 0.01 for interleukin‐1β and P < 0.05 for TNF‐α) of the steroid release was found with respect to the α‐melanotropin‐treated group. Conclusions: These results lead us to suggest that, although α‐melanotropin stimulates progesterone release in pre‐ovulatory GC, this effect is blocked by the presence of interleukin‐1β or TNF‐α.