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Biomedical subjects

W L Ledger

Publications and source records attributed to W L Ledger.

At least 19 recordsLinked to original sources
PubMed2000

Serum concentrations of dimeric inhibins, activin A, gonadotrophins and ovarian steroids during the menstrual cycle in older women.

The transition from regular ovarian cyclicity to menopause is associated with a rise in the circulating concentrations of follicle stimulating hormone (FSH), despite the maintenance of serum oestradiol concentrations during the perimenopause. The aim of this study was to compare the pattern of secretion of dimeric inhibins, activin A, gonadotrophins and steroids in regularly cycling women of 40-50 years with normal and raised early follicular phase serum FSH concentrations and young women (25-33 years) during the menstrual cycle. Blood samples were taken prospectively almost daily throughout the menstrual cycle. Women recruited were classified into three groups: (i) older women with normal FSH [(ON-FSH), day 3 FSH <8 mIU/ml, n = 10]; (ii) older women with raised FSH [(R-FSH), day 3 FSH >8 mIU/ml, n = 6] and (iii) young normal FSH (YN-FSH) women, age 25-32 years (n = 6). Cyclic patterns of serum inhibins and activin A were similar in the ON-FSH and YN-FSH groups. The R-FSH group had significantly lower concentrations of inhibin A prior to the luteinizing hormone (LH) surge and in the mid-luteal phase and lower concentrations of inhibin B in the early follicular phase compared with the ON-FSH group. Serum concentrations of activin A, progesterone and oestradiol were similar in all three groups. It is concluded from this study that the rise in early follicular phase serum FSH in older women is associated with a decrease in circulating concentrations of inhibin B in the early follicular phase. However, lower circulating concentrations of inhibin A in the luteal phase of the R-FSH group may also contribute to the rise in early follicular phase FSH concentrations during the menstrual cycle, although further studies with larger numbers are required to confirm this observation.

Activins↗
PubMed1999

Endometriosis and infertility: an integrated approach.

OBJECTIVE: To define an integrated approach to endometriosis-associated infertility. METHODS: Review of published literature with grading of evidence by quality. RESULTS: Laparoscopy remains the investigation of choice in cases of endometriosis-associated infertility and allows the possibility of surgical ablation at diagnosis. This improves fertility in minimal/mild disease, whereas danazol therapy has no benefit. Both in vitro fertilization (IVF) and superovulation with intrauterine insemination improve fertility in mild/minimal disease. Neither surgery nor medical treatment have been shown to improve fertility in moderate/severe disease. IVF with prolonged pituitary down-regulation produced by long-acting gonadotropin-releasing hormone agonists after surgical debulking offers the best hope in such cases. CONCLUSIONS: Endometriosis-related infertility should be treated as rapidly as possible with thorough investigation and the minimum delay between diagnosis and therapy.

Adult↗
PubMed1999

Dimeric inhibins and activin A in human follicular fluid and oocyte-cumulus culture medium.

The concentrations of inhibin A, inhibin B and activin A in follicular fluid and oocyte culture medium were analysed to investigate the production of these peptide hormones by ovarian granulosa cells and oocyte-cumulus complexes, as well as their potential as possible biochemical markers for oocyte quality and fertilizing capacity. Follicular fluids were collected from individual follicles during oocyte retrieval for in-vitro fertilization (IVF). Oocyte-cumulus culture media were collected after in-vitro insemination. The concentrations of dimeric inhibin A, inhibin B and activin A were measured using two-site enzyme-linked immunosorbent assays in the follicular fluid and matched oocyte culture medium. Hormone concentrations were compared with oocyte quality and fertilizing capacity. The concentration of inhibin A in follicular fluid increased while that of inhibin B decreased with increasing follicle size. Follicular fluid concentrations of inhibin A inhibin B and activin A were not significantly different in follicles with differing oocyte quality. Oocyte culture medium concentrations of activin A were significantly higher in morphologically good quality oocytes. There was no relationship between the concentrations of the three hormones and oocyte fertilizing capacity. This study confirms that follicular fluid concentrations of inhibin A may prove to be a marker of follicular growth and maturation. Higher concentrations of activin A produced by good quality oocyte-cumulus complexes suggest that activin A may play a role in oocyte maturation.

Activins↗
PubMed1999

Amniotic fluid concentrations of dimeric inhibins, activin A and follistatin in pregnancy.

OBJECTIVE: The feto-placental unit is the major source of circulating concentrations of inhibin A and activin A in human pregnancy. The aim of this study was to measure the amniotic fluid concentrations of inhibin A, inhibin B, activin A and follistatin in pregnancies bearing male and female fetuses. DESIGN AND METHOD: Amniotic fluid samples collected by amniocentesis were stored at -20 degrees C. Dimeric inhibins, 'total' activin A and 'total' follistatin were measured using specific two-site enzyme immunoassays. Samples were assayed blindly and the information on fetal sex was obtained from the cytogenetics laboratory. RESULTS: Data show that amniotic fluid concentrations of inhibin A, inhibin B and activin A gradually increase with gestation whilst concentrations of follistatin are similar between weeks 15 and 20 of pregnancy. Mean amniotic fluid levels of inhibin A and inhibin B at 16 and 17 weeks gestation and mean activin A levels at 15 and 16 weeks gestation are considerably lower in pregnancies with male (n=24) compared with female (n=28) fetuses. Levels of follistatin are not different in the male and female fetal pregnancies at any studied gestation. CONCLUSIONS: The results indicate that amniotic fluid contains high concentrations of inhibins (A and B), activin A and follistatin in early pregnancy suggesting that these hormones are produced by the fetal membranes and may be involved in the development of the fetus.

Activins↗
PubMed1998

Comparison of highly purified FSH (metrodin-high purity) with pergonal for IVF superovulation.

PURPOSE: The use of highly purified follicle-stimulating hormone (Metrodin-HP) was compared with that of a preparation containing follicle-stimulating hormone and luteinizing hormone (Pergonal) for production of superovulation in an IVF program. METHODS: We used the Oxford Fertility Unit database to identify patients undergoing their first cycle of IVF, using either Metrodin-HP or Pergonal. Patients were treated with a standardized drug protocol and were stratified by age and cause of infertility. Ovarian stimulation with either Metrodin-HP (Serono Laboratories) or human menopausal gonadotropin (hMG; Pergonal; Serono Laboratories) after pituitary desensitization commenced in the midluteal phase of the preceding cycle. Monitoring was performed by ultrasound and serum estradiol measurement prior to transvaginal oocyte recovery, followed by IVF and transfer of no more than three embryos. RESULTS: For Metrodin-HP versus Pergonal, the rates of egg retrieval (98 vs 94%), fertilization (89 vs 92%), clinical pregnancy (32.9 vs 23.4%), miscarriage (4.1 vs 4.5%), live birth (26 vs 18.5%), and ovarian hyperstimulation syndrome (5.5% vs 5.9%) were similar in both groups. The apparent increase in clinical pregnancy and live birth with Metrodin-HP did not reach statistical significance. The dosages of gonadotropins used were comparable. Estradiol levels measured on day 8 of stimulation were significantly lower in the Metrodin-HP group than in the Pergonal group, but the difference did not reach statistical significance on the day of hCG administration. Significantly more follicles (greater than 12 mm) were obtained in the Metrodin-HP group, but the numbers of eggs recovered and fertilized were similar in the two groups. CONCLUSIONS: These findings demonstrate that highly purified FSH (Metrodin-HP) is as effective and successful as hMG (Pergonal) for ovarian stimulation in a standard IVF regimen. Exogenous luteinizing hormone (LH) is not required for satisfactory ovarian stimulation in IVF. Measurement of estradiol may be less helpful in the monitoring of Metrodin-HP cycles, but the level reached on the day of hCG administration can still be used to predict, and hence avoid, ovarian hyperstimulation syndrome.

Adult↗
PubMed1998

Identification of the source of inhibins at the time of conception provides a diagnostic role for them in very early pregnancy.

PROBLEM: Early diagnosis of a complicated or poor pregnancy outcome in patients undergoing assisted reproductive technique (ART) fertility treatment could aid their counseling and management. A possible role for the inhibin superfamily as markers of early pregnancy viability was investigated. METHOD OF STUDY: To determine the source of the dimeric glycoproteins inhibin A (alpha-beta A) in early pregnancy, serial blood samples from women who became pregnant following in vitro fertilization (IVF) with fresh embryo transfer (n = 50), from women who achieved pregnancy with frozen-thawed embryos (n = 8), and from a control group of women with spontaneous conceptions (n = 7) were analyzed using a two-site enzyme-linked immunosorbent assay (ELISA). Gonadotropin-releasing hormone (GnRH) analogues are routinely used in ART treatment cycles and are recognized to be luteolytic, and hence, periconceptual administration may be deleterious to pregnancy outcome. Serum samples were obtained from 8 IVF patients who conceived during the cycle in which they had inadvertent luteal phase exposure to GnRH analogues. RESULTS: Elevated serum levels of inhibin A were detected in ongoing pregnancies from 4 weeks' gestation and increased to an initial peak at 9-10 weeks' gestation. Significantly higher levels (P < 0.05) were found in the multiple pregnancies, and nonviable clinical pregnancies had very low levels of inhibin A. Inhibin pro-alpha C was detectable at levels above normal late luteal values in singleton and multiple pregnancies arising from IVF with fresh embryo transfer. In pregnancies established without corpus luteum activity, frozen-thaw embryo replacement, the levels of pro-alpha C containing inhibins were extremely low, suggesting that the corpus luteum is the major source of the alpha monomer. In pregnancies following inadvertent periconceptual exposure to GnRH analogue, the levels of pro-alpha C were statistically significantly higher in successful pregnancies than in early pregnancy failures. CONCLUSIONS: The feto-placental unit is confirmed as the major source of inhibin A in early pregnancy, and the initially low levels and very rapid decline in inhibin A in pregnancies with embryonic failure suggest a role for this glycoprotein as a monitor of early pregnancy viability. The corpus luteum is demonstrated to be the major source of inhibin pro-alpha C in early pregnancy, and very low levels in patients with peri-implantational exposure are indicative of lytic damage and herald pregnancy failure despite luteal supplementation with progesterone.

Corpus Luteum↗
PubMed1998

Mid-follicular phase pulses of inhibin B are absent in polycystic ovarian syndrome and are initiated by successful laparoscopic ovarian diathermy: a possible mechanism regulating emergence of the dominant follicle.

The hypothalamic pulse generator of GnRH is recognized to be central to ovulatory function as evidenced by the anovulation of women with hypogonadotrophic hypogonadism due to Kallmann's syndrome or severe anorexia nervosa. LH is released from the anterior pituitary in pulses, the frequency of which is closely entrained with those of GnRH. In contrast, secretion of FSH is influenced by a number of regulatory molecules, including GnRH, estradiol, inhibin, and activin. The close temporal relationship between changes in levels of inhibin B and FSH in the mid-follicular phase suggests that the release of inhibin B by the preovulatory follicle critically regulates pituitary FSH secretion. Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders affecting ovulation, and abnormal ovarian morphology as detected by ultrasonography remains the most sensitive diagnostic marker for this disorder. The etiology of PCOS is unclear, but its effective treatment by both anti-estrogens and by exogenous FSH suggests that a primary disorder of FSH regulation may be central. To investigate the possible role of inhibin B in the pathology of PCOS, serum inhibin B levels were measured in 10 women with PCOS on cycle day 5 of a spontaneous or progestrogen-provoked bleed and compared with levels on cycle day 5 of 10 women with regular ovulatory cycles. The mean serum inhibin B levels in the PCOS patients were significantly higher at 248 (+/- 43.4) pg/mL compared with normal controls, 126 (+/- 18.6) pg/mL (P < 0.01). Ten women with clomiphene resistant PCOS and 5 normal controls consented to undergo serial blood sampling on cycle day 5. Time Series Analysis using a Fourier Transformation to analyze the power spectrum of the data revealed that in normal women there is a distinct periodicity in inhibin B levels with a clear peak detectable every 60-70 min (P < 0.05), whereas in women with ovulatory dysfunction due to PCOS, no such pattern of regular pulsatility was seen. Four women with PCOS whose anovulation was successfully treated with laparoscopic ovarian diathermy (LOD) underwent repeat venous sampling following LOD. Their serum inhibin B levels fell to the upper limit of the normal range (160 +/- 38.5) pg/mL, and pulsatility was initiated. It is possible that inhibin B pulses are being generated directly by the ovary in response to pulses of GnRH in the peripheral circulation, or indirectly in response to FSH pulses arising in the pituitary. The function of inhibin B pulses in the mid-follicular phase of the normal cycle remains to be elucidated, but the absence of the normal pulsatile pattern in women with PCOS, in conjunction with high basal levels of inhibin B arising from the multiple small follicles characteristic of the PCOS ovary, appears to reinforce the development of a large cohort of small, developmentally arrested, and ultimately atretic follicles in these patients. Initiation of normal inhibin B pulsatility by LOD in patients with polycystic ovaries appears to correlate with the post-operative onset of ovular cycles.

Diathermy↗
PubMed1997

Activin A and inhibin A as possible endocrine markers for pre-eclampsia.

BACKGROUND: Inhibin A and activin A are produced by the placenta during human pregnancy. This study aimed to measure circulating concentrations of inhibin A, pro alpha C-containing inhibins, and activin A in the serum of women with pre-eclampsia and of healthy matched control pregnant women, and to establish the molecular-weight forms of circulating inhibin A and activin A in pre-eclampsia. METHODS: In a retrospective cross-sectional study, blood samples were taken from 20 women in hospital with established pre-eclampsia, and from 20 control pregnant women attending antenatal clinics, who were matched for duration of gestation (pre-eclampsia mean 29.15 [SD 3.75] weeks; controls 29.30 [3.93] weeks), parity, and maternal age. Serum samples were analysed for inhibin A, inhibin B, pro alpha C, and activin A. Pooled samples of control (n = 3) and pre-eclampsia serum (n = 3) subsequently underwent fast protein liquid chromatographic analysis to assess the molecular-weight forms of inhibin A and activin A. Results are expressed as mean and SD for all variables measured. FINDINGS: Serum concentrations of inhibin A, activin A, and pro alpha C were significantly higher in pre-eclampsia than in control normal pregnancy (inhibin A 3.05 [1.8] vs 0.36 [0.14] ng/mL, p < 0.001; activin A 38.08 [25.88] vs 3.95 [2.32] ng/mL, p < 0.001; pro alpha C-containing inhibins 2.2 [0.81] vs 0.71 [0.33] ng/mL, p < 0.001). Inhibin B concentrations in maternal serum were not increased. Molecular-weight forms of inhibin A (32 kDa) and activin A (> 100 kDa) were similar in pre-eclampsia and normal pregnancy. The mean concentrations of hCG were 59.05 [43.98] and 16.3 [8.72] ng/mL, respectively. INTERPRETATION: Higher maternal serum concentrations of inhibin A, pro alpha C, and total activin A in pre-eclampsia than in control pregnancies could be helpful in the diagnosis of pre-eclampsia. These changes are interpreted as further evidence for trophoblast dysfunction in pre-eclampsia.

Activins↗
PubMed1997

Sequential bilateral adnexal torsion after a single cycle of gonadotropin ovulation induction with intrauterine insemination.

OBJECTIVE: To report a rare case of sequential bilateral adnexal torsion in a pregnant woman after a single cycle of gonadotropin ovulation induction with IUI. To review the literature with regards to the causation and aspects of the management of adnexal torsion, particularly after assisted conception. DESIGN: Case report. SETTING: Fertility department within a teaching hospital. PATIENT(S): A 35-year-old woman with a twin pregnancy after a cycle of gonadotropin ovulation induction and IUI. INTERVENTION(S): Gonadotropin ovulation induction with IUI; two laparotomies, salpingo-oophorectomy, stabilization of adnexa with stay suture. RESULT(S): Continuation of pregnancy until 37 weeks gestation with the abdominal delivery of healthy twins. CONCLUSION(S): The case of a woman with a multiple pregnancy and ovarian hyperstimulation syndrome after ovulation induction and IUI who developed sequential bilateral adnexal torsion is used to illustrate the risk factors and management options for adnexal torsion. Physicians should be aware of the increased incidence of adnexal torsion in the rising number of women undergoing ovulation induction in order to effect early surgical intervention and adnexal salvage. Consideration should be given to the anchoring of bulky adnexae to prevent torsion recurrence.

Adnexal Diseases↗
PubMed1997

Source of circulating levels of inhibin A, pro alpha C-containing inhibins and activin A in early pregnancy.

It is now established that the glycoprotein hormone inhibin is produced by primate granulosa cells, corpus luteum and trophoblast of human placenta. This study was designed to investigate the major source of inhibins and activin A in early pregnancy using a novel panel of assays with high specificity and sensitivity. A total of 12 women (aged 20-35 years) with singleton pregnancy undergoing first trimester (group 1: 6-8; group 2: 8-10; group 3: 10-12 weeks of gestation) termination of pregnancy (TOP) was recruited for the study. Blood samples were taken before TOP, every 15 min for the first hour and hourly for the next 3 h after TOP (total of 4 h of measurements). Circulating concentrations of inhibin A, pro alpha C, activin A, human chorionic gonadotrophin (HCG), oestradiol and progesterone were higher in early pregnancy than at any stage of the menstrual cycle. Peripheral concentrations of inhibin A and activin A were significantly decreased within the first hour in all three groups and gradually decreased to even lower concentrations within the study period. Pro alpha C concentrations decreased within the first hour and then remained unaltered during the next 3 h. Similarly, HCG, oestradiol and progesterone concentrations in circulation decreased substantially within 4 h of TOP. Correlation analyses showed a significant positive correlation (P < 0.001) between inhibin A, activin A, HCG, and oestradiol concentrations throughout the study period. In summary, this study shows that the feto-placental unit is the major source of increased circulating concentrations of inhibin A in early pregnancy. Activin A is produced by the feto-placental unit and the corpus luteum. Pro alpha C-containing inhibins are mainly secreted by the corpus luteum in early pregnancy.

Activins↗
PubMed1997

Measurement of inhibin and activin in early human pregnancy: demonstration of fetoplacental origin and role in prediction of early-pregnancy outcome.

To determine the source of the dimeric glycoproteins inhibin A (alpha-betaA) and activin A (betaA-betaA) in early pregnancy, we analyzed serial blood samples from women who became pregnant following in vitro fertilization (IVF) with fresh embryo transfer (ET; n = 52) and from women who achieved pregnancy with frozen-thawed embryos (n = 8). Elevated serum levels of inhibin A were detected in ongoing pregnancies from 4 wk gestation (13 days following ET) and increased to an initial peak at 9-10 wk gestation. Significantly higher levels (p < 0.05) were found in the multiple pregnancies, and nonviable clinical pregnancies had very low levels of inhibin A. Total activin A was detectable 14 days after ET (positive pregnancy test), and higher levels were associated with multiple gestations while rapidly falling levels heralded embryonic demise. The fetoplacental unit is thus confirmed as the major source of these glycoproteins. Inhibin pro-alphaC, which circulates in great excess as a functionally inactive monomer and as part of high molecular weight functional dimers, was detectable at levels above normal late-luteal values in singleton and multiple IVF arising from fresh ETs. With frozen-thawed embryo pregnancies, the levels of pro-alphaC-containing inhibins were extremely low, confirming that the corpus luteum of pregnancy is the major source of the alpha monomer. The initially low levels and very rapid decline in inhibin A in pregnancies with embryonic failure suggest a role for this glycoprotein as a monitor of early-pregnancy viability.

Activins↗
PubMed1996

Circulating inhibins and activin A during GnRH-analogue down-regulation and ovarian hyperstimulation with recombinant FSH for in-vitro fertilization-embryo transfer.

OBJECTIVE: We have investigated serial changes in plasma concentrations of inhibin A, inhibin B, pro alpha C and activin A in women undergoing stimulation with recombinant FSH in 'long-protocol' down-regulated cycles of IVF treatment. DESIGN: Blood samples were collected during the entire IVF treatment cycle at points coinciding with the early follicular phase of the cycle preceding treatment, pituitary down-regulation, stimulation with recombinant FSH, ovulatory triggering, and the luteal phase of the cycle. In patients who achieved conception, blood samples were also taken during the first 2 weeks of pregnancy. All samples were analysed for inhibin A, inhibin B, pro alpha C, activin A and oestradiol. PATIENTS: Fifteen women with normal ovarian function undergoing IVF treatment with tubal factor, mild endometriosis or idiopathic infertility. RESULTS: During pituitary desensitization, both inhibin A and inhibin B were significantly (P < 0.001, P = 0.002, respectively) reduced whereas levels of pro alpha C and activin A were largely unaltered. Levels of both inhibins rose markedly (P < 0.01) during FSH stimulation and a further rise in inhibin A was detected on the day after ovulatory trigger. Levels of both inhibin A and inhibin B then fell during and after oocyte pickup and continued to fall during the luteal phase. Activin A levels rose less markedly during gonadotrophin stimulation. Statistical analysis showed a high degree of correlation between the number of follicles (> 10 mm) and serum inhibin A (r = 0.65, P < 0.01) and pro alpha C (r = 0.65, P < 0.01) concentrations during the late follicular phase. CONCLUSIONS: These results indicate that ovarian production of dimeric inhibin A and B are gonadotrophin dependent, whereas activin A may have a significant gonadotrophin independent or extra-gonadal source. Inhibin A and pro alpha C may be useful markers for monitoring the effects of gonadotrophin stimulation.

Activins↗
PubMed1996

Antiphospholipid antibodies in women having in-vitro fertilization.

Antiphospholipid antibodies have an established association with pregnancy complications such as recurrent miscarriage, growth retardation, placental abruption and stillbirth but their mechanism of action is unclear. We have investigated whether antiphospholipid antibodies occur more frequently in women having in-vitro fertilization (IVF) and whether their presence is associated with the likelihood of failed implantation. We studied 240 women undergoing IVF treatment who were </=38 years and had attempted fewer than three previous IVF cycles. Antiphospholipid antibodies (anticardiolipin and antiphosphatidyl serine immunoglobulin G and immunoglobulin M) were present in 36 out of 240 (15%) of the study population and were not associated with a failed IVF cycle or miscarriage. There was no association between the cause of infertility and the presence of antiphospholipid antibodies. Antiphospholipid antibodies were not detected more frequently in women with previous attempts at IVF compared with women having their first cycle, indicating that the high incidence of these antibodies is not due to the IVF treatment. There was a strong association between the presence of antiphospholipid antibodies and intrauterine growth retardation in singleton pregnancies (P < 0.005). We recommend routine screening for the presence of antiphospholipid antibodies in women having IVF in order to identify those pregnancies at increased risk of intrauterine growth retardation.

Adult↗
PubMed1995

Successful pregnancy outcome in a renal transplant patient following in-vitro fertilization.

Renal transplantation transforms the fertility potential of women with end-stage renal failure and the prognosis for both pregnancy outcome and continuing renal function in those patients is generally good. Currently one in 50 women become pregnant following renal transplant and it may be assumed that more would welcome the chance of biological parenthood if their fertility problems, related often to tubal damage, could be overcome. We here report our experience of treating a couple with secondary infertility with in-vitro fertilization and embryo transfer where the wife is a renal transplant recipient. We believe this is the first reported case.

Adult↗
PubMed1994

Rapid diagnosis of early ectopic pregnancy in an emergency gynaecology service--are measurements of progesterone, intact and free beta human chorionic gonadotrophin helpful?

The clinical usefulness of measuring serum concentrations of progesterone, human chorionic gonadotrophin (HCG) and the free beta-subunit of HCG in distinguishing between early viable and non-viable pregnancy, before an accurate ultrasound diagnosis is possible, was evaluated in a prospective study of patients presenting to our emergency gynaecology service with a clinical suspicion of ectopic pregnancy. Patients were selected on the basis of initial HCG concentrations; samples with HCG 25-10,000 IU/l were later analysed for progesterone and free beta HCG. Of the 181 patients studied, 38 (21%) had an ectopic pregnancy, 108 (60%) had a spontaneous abortion and 35 (19%) had a viable intra-uterine pregnancy. Concentrations of HCG and free beta HCG in the group with viable pregnancies were significantly higher than in the group with ectopic pregnancy (P < 0.001) and than those destined to miscarry (P < 0.01). Progesterone concentrations were also significantly higher in the viable versus the ectopic and the spontaneous abortion groups (P < 0.001 in each case). Despite these highly significant differences there was a degree of overlap such that it was impossible to devise a cut-off level for any hormone analysed, either singly or in combination, which would offer a clinically useful predictor of outcome.

Chorionic Gonadotropin↗
PubMed1993

Immunolocalization of oestrogen and progesterone receptors in the human decidua in relation to prolactin production.

The distribution of oestrogen and progesterone receptors within the decidualized stroma of the uterus was examined in early and term human pregnancy and the results related to the effect of oestradiol and progesterone on prolactin production by decidua in vitro. In early pregnancy progesterone receptors were present in the nucleus of decidualized cells of both the capsularis and parietalis but not in glandular cells. In contrast at term progesterone receptors were located within the cytoplasm of decidual cells. Oestrogen receptors were detected only in the nucleus and were present in greater amounts in decidua capsularis than parietalis in early pregnancy, but were not detectable in term decidua. Both oestrogen and progesterone receptors were present in the nuclei of cells of arterioles within the decidua. In early pregnancy prolactin production decreased during in-vitro culture of decidua parietalis but was maintained in decidua capsularis, associated with an increase in progesterone production by the decidua capsularis. In term decidua, prolactin production in vitro was only stimulated by a combination of oestradiol and progesterone. These results suggest, firstly, that maintained decidualization and prolactin production by decidua capsularis during treatment of women in early pregnancy with the anti-progestin mifepristone is not due to an absence of progesterone receptor; secondly, there is a shift in immunoreactive progesterone receptor in decidual cells from the nucleus in early pregnancy to the cytoplasm in term pregnancy. This may indicate an alteration in the action of progesterone around the time of parturition; and thirdly, in term decidua, progesterone, apparently acting through the cytoplasmic receptor, is active in increasing prolactin production in vitro only when combined with oestradiol.

Cells, Cultured↗