Endogenous Progesterone Concentrations Research Articles

The Correlation of Endogenous Progesterone Concentration in Diestrus on Early Pregnancy Rate in Thoroughbred Mares

The aim of this project was to test the hypothesis that progesterone concentration 5 days after ovulation did not differ between pregnant and nonpregnant Thoroughbred mares on stud farms located in the Waikato region of New Zealand. A prospective cohort study was performed involving five stud farms in the Waikato region of New Zealand during the 2018 breeding season. A total of 275 mares were enrolled in the study. Mares were served by 34 individual stallions. Blood samples were taken from each mare 5 days after ovulation (D0) and measured for progesterone concentration. Early pregnancy was confirmed at D14 by transrectal palpation and ultrasonography of the mares reproductive tract. Progesterone concentration at Day 5 post-ovulation was higher in mares determined to pregnant at Day 14 of gestation than in mares determined to be non-pregnant at Day 14 (6.4 ± 3.0 ng/ml vs. 5.5 ± 3.3 ng/ml respectively; P = .02). A negative association between increasing mare age and pregnancy rate was found but mare age had no effect on progesterone concentration at D5. In this study we found that although higher serum progesterone concentration at Day 5 post ovulation was associated with a higher pregnancy rate at Day 14, no predictive or definitive minimum required progesterone concentration could be identified. Additional studies are required to determine if a synthetic progestogens can serve to supplant natural progesterone to increase pregnancy rate in naturally bred mares.

Does the HCG trigger dose used for IVF impact luteal progesterone concentrations? a randomized controlled trial

Research questionIs there an association between the ovulation trigger dose of human chorionic gonadotrophin (HCG) and endogenous progesterone production during the luteal phase? DesignThis randomized controlled four-arm study, at the Fertility Clinic, Odense University Hospital, Denmark, included women undergoing gonadotrophin-releasing hormone (GnRH) antagonist IVF treatment with ≤11 follicles ≥12 mm. Group 1–3 were triggered with 5000 IU, 6500 IU or 10,000 IU HCG, respectively, receiving 17α-hydroxyprogesterone caproate intramuscularly for luteal-phase support (LPS) to measure endogenous progesterone production. Group 4 received 6500 IU HCG trigger and vaginal progesterone. During the study, the 5000 IU and 10,000 IU HCG groups were switched from urinary to recombinant HCG, as urinary HCG was removed from market. Eight blood samples were drawn during the luteal phase. ResultsNinety-four participants completed the study. There was a significant positive association between the HCG trigger dose and the progesterone at 8 days (P < 0.001), 10 days (P < 0.001) and 14 days (P < 0.001) post-oocyte retrieval. Comparing the groups individually revealed a significant difference in progesterone concentration between low and high trigger doses at 4 days (P = 0.037) and 8 days (P = 0.007) post-oocyte retrieval and between all intervention groups at oocyte retrieval + 6 days: group 1 and 2 (P = 0.011), group 2 and 3 (P = 0.042) and group 1 and 3 (P < 0.001). Higher HCG trigger dose increased the progesterone from the individual follicle. ConclusionsIncreasing HCG trigger doses significantly increased endogenous progesterone concentration during the mid–late luteal phase.

The Correlation of Endogenous Progesterone Concentration in Diestrus on Early Pregnancy Rate in Thoroughbred Mares

The Correlation of Endogenous Progesterone Concentration in Diestrus on Early Pregnancy Rate in Thoroughbred Mares

Early pregnancy maternal progesterone administration alters pituitary and testis function and steroid profile in male fetuses

Maternal exposure to increased steroid hormones, including estrogens, androgens or glucocorticoids during pregnancy results in chronic conditions in offspring that manifest in adulthood. Little is known about effects of progesterone administration in early pregnancy on fetal development. We hypothesised that maternal early pregnancy progesterone supplementation would increase fetal progesterone, affect progesterone target tissues in the developing fetal reproductive system and be metabolised to other bioactive steroids in the fetus. We investigated the effects of progesterone treatment during early pregnancy on maternal and fetal plasma progesterone concentrations, transcript abundance in the fetal pituitary and testes and circulating steroids, at day 75 gestation, using a clinically realistic ovine model. Endogenous progesterone concentrations were lower in male than female fetuses. Maternal progesterone administration increased male, but not female, fetal progesterone concentrations, also increasing circulating 11-dehydrocorticosterone in male fetuses. Maternal progesterone administration altered fetal pituitary and testicular function in ovine male fetuses. This suggests that there may be fetal sex specific effects of the use of progesterone in early pregnancy, and highlights that progesterone supplementation should be used only when there is clear evidence of efficacy and for as limited time as necessary.

Effect of Efavirenz on Endogenous Progesterone Concentrations and Contraceptive Outcomes among Ugandan HIV Infected Women Coadministering Ethinylestradiol/Levonorgestrel.

This study assessed the effect of efavirenz mid-dose plasma concentrations on mid-luteal endogenous progesterone concentrations and contraceptive outcomes among 49 HIV infected women coadministering ethinylestradiol/levonorgestrel, including 34 HIV positive women on Highly Active Antiretroviral Therapy (HAART) and 15 HAART naïve HIV infected women, purposively selected from Mulago Hospital, Uganda. A blood sample was collected once between days 20 and 22 of each woman's menstrual cycle for measuring endogenous progesterone and efavirenz concentrations by electrochemiluminescence technology and High Performance Liquid Chromatography (HPLC), respectively. Descriptive statistical analysis and correlation and logistic regression analysis were done using SPSS v.21 and R3.1. Efavirenz showed a weak positive linear relationship with endogenous progesterone at efavirenz concentrations below 12 μg/ml. Based on serum endogenous progesterone, the observed hormonal contraceptives failure rate (24.5%) was higher than expected (maximum 8%). A higher proportion of HIV positive women on efavirenz based HAART (26.5%) was at risk of contraceptive failure than their HIV infected HAART naïve counterparts (20%) though it was not statistically significant (p = 0.63). Efavirenz mid-dose plasma concentrations seem to have no significant effect on mid-luteal endogenous progesterone concentrations and contraceptive outcomes among HIV infected Ugandan women coadministering ethinylestradiol/levonorgestrel oral pills.

Influence of progesterone on functional activity of neutrophils in threatening preterm labor

Aim of the study. To assess the influence of exogenous progesterone on the functional activity of neutrophils in patients, whose pregnancies proceeded with clinical signs of threatened abortion. Materials and methods. The material used for the study were peripheral blood neutrophils of 32 women, who were hospitalized with a diagnosis of "threatening premature labor" in the term of 22-34 weeks and whose pregnancies later ended in spontaneous preterm (group 1, 10 patients) and term (group 2, 22 patients) birth. Women of 1st and 2nd groups were comparable in age, gestational age and serum concentration of endogenous progesterone. The study was conducted in vitro. Neutrophils were isolated by settling for NBT-test and phagocytosis reaction, and by centrifugation on a double density gradient of ficoll-verografin in order to assess the formation of neutrophil extracellular traps. Neutrophils were added to a suspension of exogenous progesterone at concentrations of 10 ng/ml, 20 ng/ml, 100 ng/ml. The oxidation activity of neutrophils was measured in the spontaneous and stimulated (with Staphylococcus aureus at a concentration of 1×108 bacterial cells in 1 ml) types of NBT-test with microscopic evaluation of the results. The ability of neutrophils to form extracellular traps was evaluated in spontaneous and stimulated (with Staphylococcus aureus at a concentration of 1×108 bacterial cells in 1 ml) types of the test using color dye Hoechst 33342, followed by fluorescent microscopy. Results. Progesterone (10 ng/ml) significantly decreased spontaneous neutrophil oxidative activity [17.0% (12.0-26.0%) and 7.0% (4.0-10.0%), p&lt;0.05] in patients of group 1, but not in patients of group 2. There was no effect of progesterone at studied concentrations on stimulated neutrophil oxidative activity in women of groups 1 and 2. When 20 ng/ml progesterone was added there was a decrease in neutrophil phagocytic index in patients of group 2 [66% (55-77%) and 51% (40-69%), p&lt;0.05]. Progesterone (100 ng/ml) caused an increase in spontaneous NET-forming function in both groups and had no effect on stimulated function. Conclusions. Progesterone is able to provide various immunomodulatory effects on neutrophils of patients, whose pregnancies ended in preterm and term birth. Exogenous progesterone is able to provide various immunomodulatory effects on neutrophils of patients, whose pregnancies ended in preterm and term birth. It reduced the increased spontaneous oxidative activity of neutrophils in women with adverse pregnancy outcomes and lowered phagocytic number in patients with favorable pregnancy outcome. This drug also stimulated spontaneous NET-forming function of the cells, regardless of the pregnancy outcome.

Estrous response for progestin-based estrous synchronization protocols and subsequent pregnancy rates when using sorted semen in primiparous and multiparous beef cows

Sorted semen is more costly and often results in lower pregnancy rates than unsorted semen. Therefore, it is important to identify estrous synchronization protocols that maximize expression of estrus and AI pregnancy rates when using sorted semen. Our laboratory has observed good synchrony and AI pregnancy rates for cows synchronized with a 14-day CIDR treatment, followed by GnRH on day 16 and prostaglandin F2 (PG) on day 23. In the absence ofluteal progesterone, a 14-day CIDR treatment should result in the development of a persistent follicle. Thus, our protocol might be improved by the addition of PG on day 7 of the CIDR treatment, to ensure endogenous progesterone concentration is low and that a persistent follicle will develop and respond to GnRH given on day 16. This study evaluated the estrous response and subsequent AI pregnancy rate after synchronization of beef cows with a 14-day CIDR protocol, with an additional PG treatment given on day 7 of the CIDR treatment. A secondary objective was to evaluate the effect of time of insemination after onset of estrus on pregnancy rate when sorted semen was used.

Effect of a Nonsurgical Embryo Transfer Procedure and/or Altrenogest Therapy on Endogenous Progesterone Concentration in Mares

Endogenous progesterone levels may decline after transcervical embryo transfer in some mares. Progestogen therapy is commonly used to support endogenous progesterone levels in embryo transfer recipient mares or those carrying their own pregnancy. The goal of this study was to determine the effects of the transcervical transfer procedure and/or altrenogest therapy on luteal function in mares. Mares were assigned to one of six treatment groups: group 1 (untreated control; n = 7 cycles), group 2 (sham transfer, no altrenogest; n = 8 cycles), group 3 (sham transfer plus altrenogest; n = 8 cycles), group 4 (pregnant, no altrenogest; n = 9 mares), group 5 (pregnant plus altrenogest; n = 9 mares), and group 6 (nonpregnant plus altrenogest; n = 10 cycles). Mares in groups 4-6 were bred and allowed an opportunity to carry their own pregnancy. Blood samples were collected for 22 days beginning on the day of ovulation. Sham embryo transfer (groups 2 and 3, combined) did not result in a decline in endogenous progesterone levels compared with control mares (group 6). However, sham embryo transfer did result in luteolysis and an abrupt decline in endogenous progesterone levels in one of the 16 (6.2%) sham-transferred mares. Altrenogest therapy in sham-transferred mares (group 3) was associated with lower endogenous progesterone levels on days 10, 12, and 13 postovulation when compared with sham-transferred mares that did not receive altrenogest (group 2). Administration of altrenogest to pregnant mares (group 5) was associated with lower concentrations of endogenous progesterone from days 14 to 18 and on day 21 compared with endogenous progesterone levels in pregnant mares not administered altrenogest (group 4). In conclusion, a transcervical embryo transfer procedure can cause luteolysis in a low percentage of mares. Altrenogest therapy may be associated with a reduction in endogenous progesterone secretion, presumably mediated by a reduction in pituitary luteinizing hormone (LH) release and a decrease in luteotropic support.

Changes of Connexin43 Expression in Non‐pregnant Porcine Myometrium Correlate with Progesterone Concentration During Oestrous Cycle

Connexin43 (Cx43) is a major protein of myometrial gap junctions. The number of Cx43 gap junctions increase dramatically with the onset of labour in association with development of synchronized uterine contractions. The formation of myometrial gap junctions follows an increase in the oestrogen to progesterone ratio indicating an important role of steroid hormones in regulating Cx43 expression at term. However, no relationship has been established between the expression of Cx43 in the non-pregnant myometrium and concentration of steroid hormones during the oestrous cycle. Here, we used immunofluorescence and Western blotting to analyse the expression of Cx43 gap junctions in the myometrium of pre-pubertal pigs (n = 7) and mature pigs at pre-ovulatory (n = 7), luteal (n = 5) and late luteal (n = 3) stages of the oestrous cycle. The number of Cx43 gap junctions calculated per 1 mm(2) of the myometrial section was low in pre-pubertal pigs and significantly higher (p < 0.022) in pre-ovulatory animals. In relation to pre-ovulatory animals the number of myometrial gap junctions was significantly lower (p < 0.019) at the luteal phase and correlated with significantly higher (p < 0.005) concentration of endogenous progesterone. Phosphorylated isoforms of Cx43 protein were expressed in the myometrium of pre-pubertal pigs and mature animals at pre-ovulatory and late luteal phases, while they were down regulated at the luteal stage. These results indicate that changes of Cx43 expression in the porcine myometrium during the oestrous cycle may be regulated by progesterone concentration and may contribute to the modulation of uterine motility.

Altrenogest treatment during late pregnancy did not reduce colostrum yield in primiparous sows1

The decrease in circulating concentrations of progesterone is the lactogenic trigger in many species. The aim of the present study was to determine the effect of an orally active progestogen, altrenogest, administered in late gestation, on lactogenesis in sows. Gilts were treated with altrenogest (20 mg/d) from d 109 to 112 of gestation (ALT112, n = 6) or d 113 (ALT113, n = 8) or were not treated (control, n = 9). Colostrum production, estimated from the BW gains of the piglets, was measured during 24 h starting at the onset of parturition. Colostrum samples were collected at the onset of parturition until 48 h later. Jugular blood samples were taken from d -8 prepartum until d 3 postpartum. Altrenogest treatment extended the gestation length of ALT113 sows in comparison with control sows (116.3 vs. 114.7 d; P < 0.05). Litter size and litter weight at birth did not differ between groups (P > 0.1). Estimated colostrum yield was not reduced in altrenogest-treated sows compared with control sows (4.20 kg) and tended to be greater in ALT112 (4.73 kg) than in ALT113 sows (3.74 kg; P = 0.09). Altrenogest reduced endogenous progesterone concentrations during the 2 d prepartum in ALT113 relative to control sows (P < 0.05), likely because luteolysis occurred earlier in relation to parturition in ALT113 sows. Altrenogest reduced estradiol-17beta concentrations during the 2 d prepartum in ALT113 (P < 0.05) and ALT112 (P < 0.1) sows. Altrenogest treatment did not influence the timing of the prepartum peak of prolactin in relation to parturition. The ALT113 sows had lesser (P < 0.05) concentrations of lactose in plasma and a lesser Na:K ratio in colostrum after parturition than Control and ALT112 sows, indicating that the junctions between their mammary epithelial cells were tighter. Concentrations of colostral IgG in sows that received altrenogest tended to be less than in control sows (P = 0.08). In conclusion, altrenogest administered from d 109 to 112 or 113 of pregnancy did not affect lactogenesis in sows, possibly because the treatment delayed farrowing and main hormonal changes without affecting the relative chronology of these changes.

Relationships between Endogenous Sex Hormone Concentrations and Vascular Function in Postmenopausal Women

Differences in postmenopausal endogenous sex hormone concentrations are associated with varying risks of a growing number of common diseases. The relationships between postmenopausal endogenous sex hormone concentrations and vascular function are not well understood. We examined in postmenopausal women the relationships between endogenous sex hormone concentrations and both blood pressure (BP) and renal vascular resistance (RVR), at baseline and in response to infused angiotensin II (AngII). SUBJECTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: A total of 34 hypertensive, postmenopausal women were studied in low-sodium and/or high-sodium balance. Serum estradiol, serum progesterone, BP, and RVR were measured at baseline. BP and RVR were remeasured after AngII infusion. In low-sodium balance, the increases in systolic and diastolic BP in response to infused AngII were blunted with increased serum progesterone concentrations (P < 0.05). The increase in RVR in response to infused AngII was also blunted with increased serum progesterone concentrations (P < 0.005). The relationships between progesterone concentration and vascular response to AngII were independent of age, body mass index, and estradiol concentration. There were no significant correlations between estradiol concentration and BP or RVR response to AngII. There were no significant correlations between sex hormone concentrations and baseline BP or RVR. In high-sodium balance, there were no significant associations between sex hormone concentrations and vascular measures. In postmenopausal women in low-sodium balance, the pressor and renovascular responses to AngII are blunted with increased endogenous progesterone concentrations. Our findings suggest a role for endogenous progesterone in modulating vascular function, even within the low postmenopausal range.

Use of Omeprazole as a CYP3A Probe Drug: Effect of Sex and Menstrual Cycle Phase on CYP3A Activity in Healthy Caucasian Adults

To determine the effects of sex and menstrual cycle phase on CYP3A activity and to characterize the intraindividual variability of CYP3A, 24 Caucasian adults were given a single dose of omeprazole every 14th day for 3 months (men) or during the mid-follicular and mid-luteal phases over 3 full menstrual cycles (women). The 2-hour plasma metabolic ratio (MR) (omeprazole/omeprazole sulphone) was used as a measure of CYP3A activity. Overall mean MRs for men (2.4 +/- 1.2) and women (2.3 +/- 0.93) were not significantly different. In women, no difference in mean omeprazole MR was observed between the mid-follicular phase (2.2 +/- 0.85) and mid-luteal phase (2.4 +/- 1.0). When all data in the mid-luteal phase were stratified into 3 groups based on the progesterone concentrations (>50 nM [A], 20-50 nM [B], and <20 nM [C]), the MR of group A was significantly lower than that of B and C. The MRs of women during the mid-luteal phase were weakly correlated with progesterone concentrations (r = -0.35; P = .03). Individual coefficients of variation (CV%) in MR ranged from 8.7% to 60.2%, with a median 30.0%. No sex or menstrual cycle differences in CYP3A activity as measured by the probe drug omeprazole were seen. Higher CYP3A activity in women may be associated with higher endogenous progesterone concentrations.

The influence of the corpus luteum on ovarian follicular dynamics during estrous synchronization in goats

Ovarian follicular dynamics and fertility are unaffected by the presence or absence of a corpus luteum during synchronization of estrus with progestins in goats. On day 5 of the estrous cycle (estrus=day 0), a gestagen-containing sponge was inserted in the vagina for 11 days. To remove corpora lutea, one group of goats (CL−, n=41) received 7.5 mg of luprostiol on days 7 and 8 of the estrous cycle. The second group of goats retained the CL (CL+, n=38). Growth and development of follicles ≥4 mm in diameter were measured daily from onset of estrus to 2 days after subsequent ovulation in seven goats from each group, using rectal ultrasonography. Estrus was detected by the use of a reproductively sterilized buck and estrous does were subsequently mated. The number of waves of follicular development (CL −=3.57±0.2 versus CL+=3.14±0.14; P>0.05) did not differ between groups. The second wave of follicular development was present at the time of progesterone decline in the CL− group and neither its duration (CL−=4.8±0.4 versus CL+=5.6±0.7 days; P>0.05) nor the day of commencement of the third wave of follicular development (CL−=11.6±0.7 versus CL+=11.8±0.6; P>0.05) were altered by the concentration of endogenous progesterone. The pregnancy rate was similar between the two groups. (CL−=68.29% versus CL+=65.79%; P>0.05). Thus, in goats, ovarian follicular dynamics and fertility were not altered by the presence or absence of a corpus luteum during estrous synchronization.

Equine embryo transfer: Influence of endogenous progesterone concentration in recipients on pregnancy outcome

Equine embryo transfer: Influence of endogenous progesterone concentration in recipients on pregnancy outcome

Regulation of follicular activity and ovulation in ewes by exogenous progestagen

The success of estrus synchronization programs using progestagen sponges, particularly for fixed-time Al, varies considerably. In view of the recent evidence in cattle that exogenous progestins alter follicular dynamics, it may be that the stage of the estrous cycle at which the synchronization protocol is begun. affects the synchrony of ovulation. The goal of this study was to evaluate the effect of medroxyprogesterone acetate (MAP) intravaginal sponges on follicular dynamics, luteal function and interval to ovulation when inserted at 3 stages of the estrous cycle. Sponges were inserted for 12 d beginning on either Day 0, 6 or 12 (n=5) following ovulation. Ovarian activity was monitored using real-time ultrasound imaging during the treatment and the post-treatment estrous cycles. Information from the post-treatment cycle was used as a baseline to compare with the treatment cycle. Most ewes (79%) in the post-treatment cycle exhibited 3 follicular waves in an estrous cycle of 16 d, with the second wave follicles having smaller diameter (P <0.001). Treatment with MAP increased the number of follicular waves from 3 to 4 or 5 when sponges were inserted on Days 6 and 12, respectively. Size of the largest follicle was smaller (P >0.01) in waves in the early and middle of the 12-d MAP treatment period when compared with the last 4 days. This effect was most pronounced when endogenous progesterone concentrations were elevated concurrently with the presence of the sponge. Persistence of the ovulatory follicle was increased (P <0.001) when sponges were inserted on Day 12, the only treatment where these follicles were under the influence of MAP in the absence of functional corpora lutea. Follicles were regressing at sponge removal in the Day 6 treatment, which resulted in a delay in emergence of ovulatory follicles, the LH surge and ovulation (P < 0.08) in relation to Day 0 and Day 12. Treatment with MAP sponges does not adequately synchronize estrus and ovulation among cyclic ewes due to the different follicular patterns that result depending on the stage of cycle at the time of sponge insertion.

Factors affecting success of embryo collection and transfer in a transgenic goat program

During a goat transgenic program that took place in Israel from July 1995 to February 1996, Saanen (n = 343) and Nubian x Damascus (n = 378) crossbred goats of mixed ages were used as donors (n = 433) and recipients (n = 288). The effects of season, age, number of surgical procedures, previous hormonal treatments and ovulation rate on the number of microinjectable embryos collected were studied. Likewise, the effects of these parameters on the pregnancy rate as well as the number of embryos transplanted, endogenous progesterone concentrations and exogenous progesterone supplementation were studied in recipient does. Following superovulation with ovine follicle stimulating hormone, 85% of the does responded with 13.6 ± 5.7 (mean ± S D) ovulations/doe. Age, month and number of previous hormonal treatments significantly affected the ovulation rate. The average recovery rate was 70%, and it was affected only by the ovulation rate. Pronuclei were visualized in about 30% of the flushed embryos (including unfertilized ova), and those were microinjected with human serum albumin gene construct. About 68% of the injected embryos underwent at least one division during an overnight incubation, and those embryos were transferred, giving about 2.0 transferred embryos per ovulated donor. Of the recipients, 86% responded following synchronization with 3.1 ± 1.6 (mean ± S D) ovulations per doe. Breed and month had a significant effect on the ovulation rate. Two or three microinjected embryos were transferred to each recipient, resulting in more than a 40% pregnancy rate during September to November. Lower pregnancy rates were obtained before and after that period. By monitoring plasma progesterone concentrations in the recipients it was found that progesterone concentration was correlated with the ovulation rate. However, the pregnancy rate was not affected by progesterone concentration. During January and February, 30 to 50% of the recipients failed to develop functional corpora lutea (CL) following embryo transfer, which explained the lower pregnancy rate in those months. Of the 86 kids born 4 were transgenic.

Radioligand binding assay of progesterone receptors in the primate corpus luteum after in vivo treatment with the 3 beta-hydroxysteroid dehydrogenase inhibitor, trilostane.

We and others have detected progesterone receptors (PR) in the primate (macaque and human) corpus luteum by immunocytochemistry. However, we have been unable to measure PR in the corpus luteum by conventional ligand binding assay, presumably because high endogenous concentrations of progesterone (P) in luteal tissue prevented specific binding of radiolabeled hormone to PR during the assays. To test this hypothesis, we treated monkeys with the 3 beta-hydroxysteroid dehydrogenase inhibitor, Trilostane, to reduce levels of endogenous P before conducting binding assays for PR in luteal tissue. To obtain adequate tissue for saturation analysis, rhesus monkeys (n = 6) were superovulated by treating them with hFSH beginning at menses (day 1) for 6 days, then with hFSH and hLH (days 6-9), followed by hCG (day 10). Trilostane (600 mg) was given 5 days after hCG treatment (day 15), and binding assays were conducted 18 h later. Trilostane significantly reduced mean (+/- SE) serum levels of P from 97.8 +/- 16 to 2.7 +/- 1.3 nmol/L within 18 h (P < 0.001). Strong nuclear staining of PR was detected by immunocytochemistry in both Trilostane-treated and control (not Trilostane-treated) tissue, but ligand binding was measurable only in Trilostane-treated monkeys. Scatchard transformations of saturation curves revealed high affinity binding of [3H] R5020 in luteal cytosol and nuclear extracts with an approximate dissociation constant (Kd) of 4.8 and 1.37 nmol/L, respectively. Also, the PR-specific monoclonal antibody, JZB-39, shifted a [3H]R5020-bound luteal macromolecule on sucrose gradients. Mean cytosolic and nuclear binding of [3H]R5020 were 0.31 +/- 0.09 and 0.06 +/- 0.02 fmol/micrograms DNA, respectively. Similar binding of [3H]R5020 was demonstrated in corpora lutea obtained during spontaneous menstrual cycles after Trilostane treatment (n = 3). These results show unequivocally that the PR in macaque luteal tissue can bind P with high affinity and suggest a receptor-mediated action of P in the primate corpus luteum.

Altered concentrations of gonadotrophin, prolactin and GnRH receptors, and endogenous steroids in the abdominal testes of adult unilaterally cryptorchid rats.

Testicular descent was prevented unilaterally in newborn rats by cutting the gubernaculum testis. At 100 days of age, the number of Leydig and Sertoli cells per testis, the concentration of receptors for LH, FSH, prolactin and GnRH, and endogenous concentrations of progesterone and testosterone were determined. The weight of the abdominal testes was reduced by 80%, but in spite of this they contained as many Sertoli (32.8 +/- 1.3 X 10(6), mean +/- s.e.m., n = 6) and Leydig (28.2 +/- 1.7 X 10(6) cells as did scrotal testes (32.1 +/- 2.5 X 10(6) and 24.3 +/- 1.2 X 10(6) respectively). The numbers of receptors for LH (3.2 +/- 0.2 and 1.0 +/- 0.2 pmol/testis, mean +/- s.e.m., n = 11), FSH (358 +/- 11.0 and 96.3 +/- 12.6 fmol/testis) and prolactin (535 +/- 32.7 and 92.4 +/- 13.2 fmol/testis) were reduced (P less than 0.001) in abdominal testes, but the number of GnRH receptors was unaffected (8.9 +/- 1.4 and 12.1 +/- 1.8 fmol/testis, n = 6). Testicular testosterone concentration (30.9 +/- 4.4 vs 15.4 +/- 3.2 ng/g, n = 11, P less than 0.001), but not that of progesterone (0.87 +/- 0.10 vs 1.01 +/- 0.21 ng/g), was decreased in abdominal testes. The decreased receptor and androgen values reflect functional disturbances in the abdominal testes. The changed local milieu within abdominal testes may reduce hormone receptor concentrations which are then involved in the observed Leydig cell dysfunction.

Inhibition of androgen metabolism in stroma and epithelium of the human benign prostatic hyperplasia by progesterone, estrone, and estradiol.

It has been shown that progesterone, estrone, and estradiol are present in significant amounts in the human benign prostatic hyperplasia (BPH). Therefore it was of interest to determine the inhibitory effect of these steroids on the 5 alpha-reductase and 3 alpha (beta)-hydroxysteroiddehydrogenase (HSDH) activities, the enzymes responsible for the conversion of testosterone to 5 alpha-dihydrotestosterone (DHT), and DHT to 3 alpha (beta)-androstanediols, respectively. The enzyme inhibition was analyzed in vitro by measuring the 5 alpha-reductase in the presence of either progesterone, estrone, or estradiol, using testosterone as substrate. The DHT was used as substrate for HSDH. The metabolites were quantified by t.l.c. The main results were as follows: (1) Concerning 5 alpha-reductase in BPH, the mean inhibitor constants (KI; microM) of progesterone, estrone, and estradiol were 0.11, 15.5, and 5.1, respectively. (2) Analyzing epithelium and stroma of BPH separately, the inhibition of 5 alpha-reductase resulted in nearly identical KI's. (3) Concerning HSDH in BPH, the mean KI's of progesterone, estrone, and estradiol were 169, 63, and 192, respectively. (4) Analyzing epithelium and stroma of BPH separately, the inhibition of HSDH led to nearly identical KI's. (5) The kinetic parameters (KM, Vmax) of the 5 alpha-reduction of progesterone and testosterone were nearly identical. These results led to the suggestion that the endogenous concentrations of progesterone, estrone, and estradiol have no significant inhibitory effect on the 5 alpha-reductase and HSDH in vivo. Furthermore, the nearly identical inhibitor constants found for both enzymes in epithelium and stroma of BPH indicate that in both compartments the 5 alpha-reductase and HSDH are qualitatively identical.

Subcellular progesterone in human myometrium during late pregnancy.

Samples of myometrium were obtained from twenty-two patients undergoing caesarian sections for various obstetric indications. The myometrium was homogenized and divided into four subcellular fractions (crude nuclear, mitochondrial, microsomal and cytosol). The concentration of endogenous progesterone in these fractions was determined by radioimmunoassay. In addition the concentration of oestrone and oestradiol of fifteen cytosolic fractions was determined. The subcellular concentration of progesterone (pg/mg protein) in human myometrium was higher in samples taken during labour than in samples taken at elective caesarian sections. This finding was statistically significant in the crude nuclear (P less than 0.005) and the microsomal (P less than 0.05) fractions. The absolute concentration of progesterone was lowest in the nuclear and highest in the microsomal fraction. The relative progesterone concentrations in the four subcellular fractions were the same in both groups. The data show that there is no significant decrease in myometrial progesterone associated with labour in man. The mean concentration of oestrone was higher than the mean oestradiol concentration in the cytosol fraction of human myometrium in late pregnancy. This study shows that a completely different oestrogen ratio exists in myometrium than in plasma.