Increased Serum Progesterone Concentrations Research Articles

Functioning of P-Glycoprotein during Pregnancy in Rabbits

The level P-glycoprotein (Pgp) in organs of pregnant rabbits and its content and activity in the placental barrier at different stages of pregnancy were studied. An increase in Pgp content in the jejunum on days 7, 14, 21, and 28 of pregnancy in comparison with this parameter non-pregnant females was revealed by ELISA; in the liver, Pgp content was higher on day 7 and tended to increase on day 14; in the kidney and cerebral cortex, Pgp content was higher on day 28 of pregnancy in parallel with an increase in serum progesterone concentration. We also observed a decrease in Pgp content in the placenta on days 21 and 28 of pregnancy in comparison with day 14 and a decrease in Pgp activity in the placental barrier, which was confirmed by enhanced penetration of fexofenadine (Pgp substrate) through the barrier.

Comparison of pregnancy outcomes following the transfer of early-developmental stage embryos and blastocysts produced by somatic cell nuclear transfer in Camelus dromedarius

The embryonic stage, site of embryo transfer in the reproductive tract of the surrogate, and embryo transfer method are important for the successful production of offspring. In the present study, there was comparison of pregnancy rates in camels following the surgical transfer of early-developmental stage embryos at Day 2 and transvaginal transfer of blastocysts at Day 7. Embryos were produced by somatic cell nuclear transfer using in vivo-matured oocytes and ear fibroblasts as donor cells. A total of 305 oocytes were collected from 27 donors, among which 275 oocytes were in metaphase II. In Group A, 110 oocytes were reconstructed, 78 fused oocytes were cultured for 2 days, and 37 early-developmental stage embryos were transferred into 13 surrogates. In Group B, 165 oocytes were utilized, 117 fused oocytes were cultured for 7 days, and 24 blastocysts were trans-vaginally transferred into 12 surrogates. Pregnancy was determined when there was an increase in serum progesterone concentrations and was confirmed using real-time ultrasonography. Microsatellite analysis was performed to confirm the parentage of offspring. Two live births occurred in Groups A and B (live birth rate of 15.4% and 16.7%, respectively). Results indicate both early-developmental stage embryos and blastocysts produced by somatic cell nuclear transfer using in vivo-matured oocytes can lead to live births in camel with similar efficiency. It, therefore, is recommended that trans-vaginal blastocyst transfer be utilized for camels considering the pregnancy and live birth rates, ease of the transfer procedure and comfort and safety of surrogates.

Administration of nerve growth factor-β to heifers with a pre-ovulatory follicle enhanced luteal formation and function and promoted LH release

The objective of this study was to determine the effects of bovine nerve growth factor-β (NGF) on pre-ovulatory follicle vascular area, LH release, ovulation, and luteal function when administered systemically to heifers. Post-pubertal Holstein heifers (n = 12) received an intravaginal progesterone-releasing device (CIDR) and GnRH agonist (100 μg IM). The CIDR was removed 5 d later, and heifers were given dinoprost (25 mg IM) at CIDR removal and 24 h later, followed by a second dose of GnRH agonist 48 h later. Heifers were randomly assigned to treatments using a cross-over design. For example, heifers assigned to NGF (250 μg reconstituted in 12 mL PBS IM) in replicate 1 were assigned to control (12 mL PBS IM) in replicate 2. Transrectal ultrasonography was performed before treatment and repeated every 4 h up to 32 h to determine the pre-ovulatory follicle diameter, vascular area, and ovulation. Serum samples were obtained to assess LH concentrations during the periovulatory period and every 2 d post-ovulation for measuring progesterone concentrations. A subset of heifers had luteal biopsies performed on days 9 (n = 6 per treatment) and 14 (n = 6 per treatment) post-ovulation to count luteal cell numbers and measure relative mRNA abundance for steroidogenic and angiogenic enzymes and LH receptor. Treatment with NGF increased pre-ovulatory follicle diameter (P = 0.02) and serum LH concentrations (P = 0.03) but did not affect time to ovulation (P = 0.42). Heifers treated with NGF had increased serum progesterone concentrations in the subsequent luteal phase (P = 0.03), but no change in vascular area of the follicle (P = 0.16) or CL (P = 0.20). Heifers treated with NGF had a greater number of small luteal cells (P < 0.01) and a tendency for increased LH receptor (LHR) mRNA abundance in the CL (P = 0.10). There was also increased steroidogenic acute regulatory protein (STAR; P = 0.05) and a tendency for increased cytochrome P450 family 11 (CYP11A1; P = 0.10) mRNA abundance in the CL of NGF-treated heifers. There was decreased prostaglandin E2 synthase (PGES; P = 0.03) and its receptor (PGER; P = 0.05) mRNA abundance and a tendency for decreased cytochrome P450 family 17 subfamily A member 1 (CYP17A1; P = 0.08) and hydroxysteroid 17-beta dehydrogenase (HSD17B; P = 0.06) mRNA abundance in the CL of NGF-treated heifers. Administration of NGF improved CL function in heifers potentially as a result of increased LH release.

Abstract 589: Circulating progesterone is associated with increased postmenopausal breast cancer risk: B~FIT cohort

Abstract BACKGROUND: Epidemiologic data provide compelling evidence of the association between elevated endogenous estrogens and androgens and increased postmenopausal breast cancer risk. However, the role of progesterone remains largely unexplored, primarily due to limitations in assay sensitivity and precision of progesterone measurements at low concentrations in postmenopausal women. Recently identified progesterone metabolites may provide etiologic insights as experimental data suggest that relative changes in concentrations of 5-α dihydroprogesterone (5αP) and 3-α dihydroprogesterone (3αHP) reflect cancer promoting and cancer inhibiting properties, respectively. METHODS: We developed a sensitive and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay and quantified prediagnostic levels of progesterone/progesterone metabolites in a case-cohort study within the Breast and Bone Follow-up to the Fracture Intervention Trial (B~FIT) including 405 breast cancer cases diagnosed during follow-up and a subcohort of 495 postmenopausal women not using exogenous hormones at blood draw. Multivariable adjusted hazard ratios (HR) and 95% confidence intervals (CIs) were estimated using Cox regression and linearity was assessed using splines. RESULTS: Hormone concentrations among women in the subcohort were on average 4.6 pg/mL (range 2.3-21.6) for progesterone; all measured values were above the assay detection limit. Women with higher circulating progesterone levels had an elevated postmenopausal breast cancer risk [HR (95% CI) per 10 pg/mL increase in progesterone: 1.18 (0.99-1.41)]. This association was linear in a 5-knot spline and strengthened [1.24 (1.03-1.49)] in models excluding women who reported current use of tamoxifen/raloxifene. Higher levels of 5αP relative to 3αHP were associated with a 4% increased postmenopausal breast cancer risk [per unit increase in ratio: 1.04 (1.00-1.07)]. For the individual metabolites, higher levels of both 5αP [per 10 pg/mL increase: 1.04 (0.93-1.18) and 3αHP [per 3 pg/mL increase: 1.11 (0.999-1.24)] were associated with elevated risk. All associations remained after adjustment for circulating estrogen levels. CONCLUSIONS: Our prospective data suggest that postmenopausal women with increased serum progesterone concentrations, measured using a highly sensitive LC-MS/MS assay, are at increased risk of breast cancer. Consistent with experimental studies, higher levels of 5αP relative to 3αHP were indicative of increased breast cancer risk. Unlike experimental studies, our data do not suggest that endogenous concentrations of 3αHP are associated with reduced breast cancer risk; instead both metabolites were associated with elevated risk. The identification of these risk-related progesterone metabolites supports the need for additional research regarding their role in the etiology of breast cancer. Citation Format: Britton Trabert, Doug C. Bauer, Louise A. Brinton, Diane S. Buist, Jane A. Cauley, Cher M. Dallal, Gretchen L. Gierach, Roni T. Falk, Trisha F. Hue, James V. Lacey, Andrea Z. LaCroix, Jeffrey A. Tice, Xia Xu. Circulating progesterone is associated with increased postmenopausal breast cancer risk: B~FIT cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 589.

Abiraterone acetate, exemestane or the combination in postmenopausal patients with estrogen receptor-positive metastatic breast cancer

Androgen receptor (AR) signaling and incomplete inhibition of estrogen signaling may contribute to metastatic breast cancer (MBC) resistance to a nonsteroidal aromatase inhibitor (NSAI; letrozole or anastrozole). We assessed whether combined inhibition of androgen biosynthesis with abiraterone acetate plus prednisone and estradiol synthesis with exemestane (E) may be of clinical benefit to postmenopausal patients with NSAI-pretreated estrogen receptor-positive (ER+) MBC. Patients (N = 297) were stratified by the number of prior therapies for metastatic disease (0-1 versus 2) and by prior NSAI use (adjuvant versus metastatic), and randomized (1 : 1 : 1) to receive oral once daily 1000 mg abiraterone acetate plus 5 mg prednisone (AA) versus AA with 25 mg E (AAE) versus 25 mg E alone (E). Each treatment arm was well balanced with regard to the proportion of patients with AR-positive breast cancer. The primary end point was progression-free survival (PFS). Secondary end points included overall survival, clinical benefit rate, duration of response, and overall response rate. There was no significant difference in PFS with AA versus E (3.7 versus 3.7 months; hazard ratio [HR] = 1.1; 95% confidence interval [CI] 0.82-1.60; P = 0.437) or AAE versus E (4.5 versus 3.7 months; HR = 0.96; 95% CI 0.70-1.32; P = 0.794). Increased serum progesterone concentrations were observed in both arms receiving AA, but not with E. Grade 3 or 4 treatment-emergent adverse events associated with AA, including hypokalemia and hypertension, were less common in patients in the E (2.0% and 2.9%, respectively) and AA arms (3.4% and 1.1%, respectively) than in the AAE arm (5.8% for both). Adding AA to E in NSAI-pretreated ER+ MBC patients did not improve PFS compared with treatment with E. An AA-induced progesterone increase may have contributed to this lack of clinical activity. NCT01381874.

7 OESTRAL RESPONSE AND FERTILITY IN DAIRY COWS TREATED WITH PROGESTERONE FOR 6 DAYS PRIOR TO OESTRUS SYNCHRONIZATION WITH PROSTAGLANDIN F2α

The present study tested whether the increase in serum progesterone concentrations for 6 days before oestrus synchronization with prostaglandin F2α (PGF2) increases oestral response, pregnancy rate, and reduces the incidence of twin births in dairy cattle. Seven hundred and eighty-three first-service dairy cows were synchronized with 2 injections of PGF2 14 days apart, starting on Day 35 postpartum. Six days before the second PGF2 injection, cows were assigned to 2 groups: P4 and control. The P4 group (n = 387) received a progesterone-releasing intravaginal device and an intramuscular injection of 500 mg of progesterone. The control group (n = 396) did not receive the progesterone-releasing intravaginal device or progesterone injection. Cows were inseminated 12 h after exhibiting oestrus. Pregnancy diagnosis was performed 40 and 45 days after insemination by rectal palpation and the cumulative pregnancy rate on Day 90 postpartum was determined retrospectively through the individual records. The response to the progesterone treatment varied according to the parity of the cows (P &lt; 0.05). Thus, progesterone administration improved the percentage of cows detected in oestrus in multiparous [192/255 (75.2%) v. 161/267 (60.2%)] but not in primiparous [93/132 (70.4%) v. 90/129 (69.7%)] cows. Progesterone treatment increased pregnancy rate in multiparous [53/192 (27.6%) v. 27/161 (16.7%)] but not in primiparous cows [25/93 (26.8%) v. 29/90 (32.2%)]. Likewise, progesterone administration increased the cumulative percentage of pregnant cows on day 90 postpartum in multiparous [149/255 (58.4%) v. 129/267 (48.3%)] but not in primiparous cows [77/132 (58.3%) v. 82/129 (63.5%)]. The incidence of twin births was lower (P = 0.07) in cows treated with progesterone [1/74 (1%)] than in the control group [4/53 (7%)]. It is concluded that progesterone administration before oestrus synchronization with PGF2 in first service dairy cows improves oestral response, increases pregnancy rate, and percentage of pregnant animals on Day 90 postpartum in multiparous cows, but not in primiparous cows, and decreases the incidence of twin births. This research was supported by PAPIIT-UNAM research grant (IN219811-3).

Up-regulation of lipogenic enzyme genes expression in inguinal white adipose tissue of female rats by progesterone

Contradictory results have been published regarding the influence of progesterone on lipids metabolism in adipose tissue. The aim of the present work was to elucidate whether progesterone administration in the setting of an experimental model influences lipogenic enzyme genes expression, body and adipose tissue mass. The results presented here indicate that the elevated blood progesterone concentration was associated with significant increase in lipogenic enzyme genes expression in inguinal adipose tissue of females. The rise in the expression of lipogenic enzyme genes was associated with an increase in sterol regulatory element binding transcription factor 1 (Srebf1) and S14 genes expression. Mifepristone, a specific antagonist of progesterone receptor, abolished progesterone's effect on body mass, inguinal fat mass, and lipogenic enzyme genes expression in inguinal adipose tissue. No significant changes were found in the expression of lipogenic enzyme genes, Srebf1 and S14 genes in perirenal white adipose tissue of females. The elevated blood progesterone concentration was associated with the increase in body and inguinal white adipose tissue mass of females. In males, elevated blood progesterone concentration had no effect on the lipogenic enzyme genes expression and on body and fat mass.In conclusion, we demonstrate that a chronic increase in serum progesterone concentration in females was associated with up-regulation of lipogenic enzyme genes expression in inguinal adipose tissue. Up-regulation of Srebf1 and S14 genes expression following progesterone administration suggests that products of these genes might be involved in the regulation of lipogenic enzyme genes expression by progesterone. The stimulatory effect of progesterone on lipogenic enzyme genes expression in inguinal adipose tissue seems to be specific as it was reversed by specific antagonist of progesterone receptor.

Comparison of progesterone-based protocols with gonadotropin-releasing hormone or estradiol benzoate for timed artificial insemination or embryo transfer in lactating dairy cows

The objective was to compare two protocols for synchronizing ovulation in lactating Holstein cows submitted to timed AI (TAI) or timed ET (TET). Within each farm (n = 8), cows (n = 883; mean ± SEM 166.24 ± 3.27 d postpartum, yielding 36.8 ± 0.34 kg of milk/d) were randomly assigned to receive either: 1) an intravaginal progesterone insert (CIDR®) with 1.9 g of progesterone + GnRH on Day -10, CIDR® withdrawal + PGF2α on Day -3, and 1 mg estradiol cypionate on Day -2 (treatment GP-P-E; nTAI = 180; nTET = 260); or 2) a CIDR® insert + 2 mg estradiol benzoate on Day -10, PGF2α on Day -3, CIDR® withdrawal + 1 mg estradiol cypionate on Day -2 (treatment EP-P-E; nTAI = 174; nTET = 269). Cows were subsequently randomly assigned to receive either TAI on Day 0 or TET on Day 7. Serum progesterone concentration on Day -3 was greater in GP-P-E than in EP-P-E (2.89 ± 0.15 vs 2.29 ± 0.15 ng/mL; P < 0.01), with no significant effect of group on serum progesterone on Day 7. Compared to cows submitted to TAI, those submitted to TET had greater pregnancy rates on Day 28 (44.0% [233/529] vs 29.7% [105/354]; P < 0.001) and on Day 60 (37.6% [199/529] vs 26.5 [94/354]; P < 0.001). However, there were no effects of treatments (GP-P-E vs EP-P-E; P > 0.10) on synchronization (87.0% [383/440] vs 85.3% [378/443]), conception (TAI: 35.3% [55/156] vs 33.8% [50/148]; TET: 50.7% [115/227] vs 51.3% [118/230]) and pregnancy rates on Days 28 (TAI: 30.5% [55/180] vs 28.7% [50/174]; TET: 44.2% [115/260] vs 43.9% [118/269]) and 60 (TAI: 27.2% [49/80] vs 25.9% [45/174]; TET: 38.8% [101/260] vs 36.4% [98/269]). In conclusion, GP-P-E increased serum progesterone concentrations on Day -3, but rates of synchronization, conception, and pregnancy were not significantly different between cows submitted to GP-P-E and EP-P-E protocols, regardless of whether they were inseminated or received an embryo.

Effect of increasing progesterone concentration from Day 3 of pregnancy on subsequent embryo survival and development in beef heifers

Higher systemic progesterone in the immediate post-conception period is associated with an increase in embryonic growth rate, interferon-tau production and pregnancy rate in cattle. The objective of this study was to examine the effect of increasing progesterone concentration on Day 3 on subsequent embryo survival and development. Oestrus (Day 0) was synchronised in beef-cross heifers (n=210) and approximately two-thirds of the heifers were inseminated with semen from a proven sire, while the remainder were not inseminated. In order to produce animals with divergent progesterone concentrations, half of the animals received a progesterone-releasing intravaginal device (PRID) on Day 3 of the oestrous cycle, which was left in situ until slaughter. The four treatment groups were: (i) pregnant, high progesterone; (ii) pregnant, normal progesterone; (iii) non-pregnant, high progesterone; and (iv) non-pregnant, normal progesterone. Animals were blood-sampled twice daily from Days 0 to 8 and once daily thereafter until slaughter on Days 5, 7, 13 or 16, corresponding to the 16-cell stage, the blastocyst stage, the beginning of elongation and the day of maternal recognition of pregnancy, respectively. Embryos were recovered by flushing the tract with phosphate-buffered saline and characterised by stage of development and, in the case of Days 13 and 16, measured. Data were analysed by mixed models ANOVA, Chi-square analysis and Student's t-test where appropriate. Insertion of a PRID on Day 3 increased (P<0.05) progesterone concentrations from Day 3.5 onwards. There was no difference between treatments in the proportion of embryos at the expected stage of development on Days 5 or 7 (P>0.05). While not significantly different, the proportion of viable embryos recovered was numerically greater in the high progesterone group on both Day 13 (58 v. 43%) and Day 16 (90 v. 50%). Elevation of progesterone significantly increased embryonic length on Day 13 (2.24+/-0.51 mm v. 1.15+/-0.16 mm, P=0.034) and Day 16 (14.06+/-1.18 cm v. 5.97+/-1.18 cm, P=0.012). In conclusion, insertion of a PRID on Day 3 of the oestrous cycle increased serum progesterone concentrations on subsequent days, which, while having no phenotypic effect on embryonic development on Days 5 or 7, was associated with an increase in embryonic size on Days 13 and 16.

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.

Fetal and Neonatal Exposure to Nicotine Disrupts Ovarian Function and Fertility in Adult Female Rats

Women born to mothers who smoked during pregnancy have been shown to have impaired fertility, although the mechanisms underlying this association are unknown. Nicotine administration in adult animals has adverse effects on the ovary and uterus; however, the effects of fetal exposure to nicotine on postnatal ovarian function have not been determined. The goal of this study was to assess the effect of fetal and neonatal exposure to nicotine on ovarian function and fertility of the offspring. Nulliparous female Wistar rats were given 1 mg.kg-1.d-1 nicotine bitartrate, subcutaneously for 14 d prior to mating, during pregnancy and throughout lactation until weaning. Measures of fertility, breeding success, and serum levels of ovarian steroid hormones in offspring were assessed at 4 and 6 mo of age. Fetal and neonatal exposure to nicotine significantly increased the time to pregnancy as the animals aged. Similarly, evidence of altered ovarian steroidogenesis including increased serum progesterone concentrations and a decreased estrogen:progesterone ratio was observed in 6-mo-old animals. We conclude that fetal and neonatal exposure to nicotine results in delayed ovarian dysfunction in adult female offspring.

Effects of Human Chorionic Gonadotrophin Administration on Artificial Insemination Pregnancy Rates in Beef Heifers

The objectives of this study were to determine whether administering human chorionic gonadotropin (hCG) at 5 d post-AI improves fertility in beef heifers by increasing serum progesterone concentrations. Nulliparous crossbred beef heifers from separate breeding seasons [early (EBH; n = 48) and late (LBH; n = 48) breeding heifers] were stratified by BW, body condition score (BCS), and age within breeding season and randomly allotted to one of two treatments. All heifers were synchronized for standing estrus with the 7-11 MGA®-Select Synch protocol. Control heifers received a saline injection (3 mL; i.m.) and heifers in the treatment (hCG) group received hCG (3300 IU; i.m.) at 5 d post-AI. Blood samples were collected on d −35 and −28 to determine estrous cycling rates and for 5 consecutive d (beginning 4 d post-AI) for serum progesterone analysis. No treatment × breeding season interaction occurred; therefore, EBH and LBH data were pooled to analyze for main effects. First-service conception rates, estrous cycling status, and estrous cycling response were similar (P>0.10) for control vs hCG heifers. Serum progesterone concentrations were similar (P>0.10) on d 4, 5, and 6 post-AI for control vs hCG heifers; however, heifers receiving hCG had greater (P<0.05) serum progesterone concentrations on d 7 and 8 of the estrous cycle post-AI than did control heifers. Administration of hCG at 5 d post-AI increased serum progesterone concentrations by d 7 of the estrous cycle post-AI; however, AI pregnancy rates did not improve for beef heifers receiving hCG, suggesting that elevating progesterone synthesis does not improve fertility in beef heifers.

Rescue of the corpus luteum and an increase in luteal superoxide dismutase expression induced by placental luteotropins in the rat: action of testosterone without conversion to estrogen.

The superoxide radical and its scavenger, superoxide dismutase (SOD), play important roles in the regulation of corpus luteum function. The present study was undertaken to investigate whether SOD is related to pregnancy-induced maintenance of corpus luteum function. Placentae obtained from rats on Day 12 of pregnancy were incubated for 24 h, and the supernatant was used as placental luteotropins. Pseudopregnant rats were given the placental incubation medium from Day 9 to Day 12 of pseudopregnancy. The treatment significantly increased serum progesterone concentrations on Day 12 of pseudopregnancy. Both activities and mRNA levels of copper-zinc SOD (Cu,Zn-SOD) and manganese SOD (Mn-SOD) in the corpus luteum were also increased on Day 12 of pseudopregnancy. Treating the placental incubation medium with charcoal significantly eliminated the stimulatory effects of placental incubation medium on serum progesterone concentrations and luteal Mn-SOD expression, but not on Cu,Zn-SOD expression. The inhibitory effect of the charcoal treatment on luteal Mn-SOD expression was reversed by supplementation with testosterone or dihydrotestosterone (DHT), but serum progesterone concentrations were recovered only by DHT. Testosterone or DHT alone had no effect on serum progesterone concentrations and luteal SOD expression. In conclusion, placental luteotropins increased SOD expression in the corpus luteum and stimulated progesterone production, suggesting that SOD is involved in the maintenance of the corpus luteum function by placental luteotropins. In addition, androgen, with other placental luteotropins, acted to stimulate progesterone production and Mn-SOD expression in pseudopregnant rats.

Control of the weaning-to-estrus interval in sows using gonadotropins and prostaglandins during lactation.

Two experiments were conducted to examine the effectiveness of various strategies using gonadotropins to induce ovulation during lactation as a means of controlling the weaning-to-estrus interval in sows. The objective of Exp. 1 was to examine the efficacy of various gonadotropin regimens for induction of ovulation during lactation. Primiparous (n = 60) and multiparous (n = 83) crossbred sows were assigned, before farrowing, to one of four treatments: no injection (control); 1,000 IU hCG on d 0 (hCG-0; d 0 = day of farrowing); P.G. 600 + 1,000 IU hCG 4 and 7 d after farrowing, respectively (hCG-7); or P.G. 600 + 1,000 IU hCG 11 and 14 d after farrowing, respectively (hCG-14). Sows were weaned on 18 +/- 2 d after farrowing and monitored daily for estrus via exposure to mature boars. The criterion for determining the induction of ovulation was a sustained increase in serum progesterone concentrations above 4.0 ng/mL. The most consistent response to exogenous gonadotropins was on d 0, with an 80% response in primiparous sows (12/15) and a 71% response in multiparous sows (15/21). Weaning-to-estrus intervals for multiparous sows were longer (P = .05) for hCG-14 and hCG-7 than for control and hCG-0 sows. Weaning-to-estrus intervals for primiparous sows were longer (P = .05) for the hCG-14 than for the hCG-0 treatment. The objective of Exp. 2 was to ascertain the effects of postpartum treatment with hCG (1,000 IU) on d 0 and PGF2alpha (10 mg) at d 14 on the weaning-to-estrus interval in multiparous sows weaned at d 14 after birth. Before farrowing, sows (n = 60) were randomly assigned to one of four treatments: positive control, weaning at d 21; negative control, weaning at d 14; hCG within 24 h after farrowing, weaning at d 14; or hCG within 24 h after farrowing and PGF2alpha at weaning, weaning at d 14. Weaning-to-estrus intervals were longer (P = .05) in sows receiving PGF2alpha than in the other treatments. Results indicate that it is possible to induce ovulation immediately after farrowing, using a single injection of hCG, and this strategy can be used to uncouple weaning from the resumption of reproductive activity. However, the administration of PGF2alpha at 14 d after farrowing did not consistently cause regression of the induced corpora lutea.

Utility of serum progesterone and prolactin analysis for assessing reproductive status in the Asian elephant (Elephas maximus).

Concentrations of serum progesterone and prolactin were assessed during the perioestrous period and throughout gestation in the Asian elephant (Elephas maximus) as a means of generating information of potential use to managers. In > 95% of perioestrous periods (n=35), behavioural oestrus (as determined by bull interest, mounting and/or breeding) coincided with the onset of increased serum progesterone concentrations at the beginning of the luteal phase and continued through Day 7 (Day 1 = first significant serum progesterone rise). Within individuals, 1- to 2-day transient decreases (P < 0.05) in serum progesterone occurred between Days 2 and 9. Notably, no sexual behaviour was observed in any female after this transient fall in progesterone. Prolactin concentrations fluctuated randomly throughout the perioestrous period, with no clear pattern. During the study, four females conceived (one conceived twice), and two delivered three viable offspring. Serum progesterone was elevated above baseline throughout gestation, and then declined precipitously 2-3 days before parturition. Serum prolactin concentrations were significantly elevated above baseline (P < 0.05) after 5-6 months of gestation and remained high until after parturition. This study confirms that serum progesterone and prolactin analyses are useful tools for monitoring the reproductive status of Asian elephant females. Specifically, the transition from low to high progesterone secretion during the late interluteal/early luteal phase is predictive of oestrus and can be used to coordinate breeding efforts. Pregnancy can be confirmed by elevated serum prolactin after 6 months postbreeding, whereas the late gestational decrease in progesterone is predictive of impending parturition.

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 (> 1 ng/l) on or before the day of human chorionic gonadotrophin (HCG) injection on the outcome of women receiving gonadotrophin-releasing hormone analogue (GnRHa)/human menopausal gonadotrophin (HMG) for ovarian stimulation prior to intracytoplasmic sperm injection (ICSI) was evaluated. A total of 1275 ICSI cycles were analysed retrospectively. In 53 cycles (4.5%), serum progesterone concentrations were > 1 ng/ml. Patients in the high progesterone group had significantly higher oestradiol and luteinizing hormone concentrations on the day of HCG injection. The characteristics of the cumulus-corona cell complexes and the nuclear maturity of the oocytes were similar in the groups of patients with high and low serum progesterone levels. Fertilization and cleavage rates as well as embryo quality were not different in the two groups. No difference in implantation or clinical pregnancy rates was observed between the high progesterone and low progesterone groups. Moreover, the cumulative exposure to progesterone during the follicular phase, as expressed by the area under the curve (AUC), and the duration of exposure to high serum progesterone levels (> 1 ng/ml) were not significantly different between pregnant and non-pregnant women in the high progesterone group. We conclude that in ICSI cycles pretreated with GnRHa, increased serum progesterone concentrations on or before the day of HCG injection do not affect ICSI outcome.

Effects of chronic treatment with a gonadotrophin-releasing hormone agonist on peripheral concentrations of FSH and LH, and ovarian function in heifers

The effect of chronic treatment with a gonadotrophin-releasing hormone agonist (GnRHa) on ovarian function in cattle was investigated by injecting heifers i.m. twice a day with saline, 5 micrograms GnRHa (Buserelin) or 10 micrograms GnRHa (n = 7) for 21 days. Blood samples were taken twice a day during the treatment period, and then three times a day for 7 days and once daily for a further 4 days. Frequent samples were also collected on day 1, day 10 and day 21 of treatment. The ovaries of all heifers were examined daily using real-time ultrasonography throughout the experimental period. No significant differences in the response were observed between two doses of GnRHa. The first GnRHa injection produced a large LH and FSH surge and this acute response was still present by day 21 of treatment, but both the magnitude and duration of response were significantly attenuated (P < 0.01). After an initial increase, LH returned to the basal concentration, which was maintained until the termination of treatment, when concentrations increased significantly, with a preovulatory surge occurring approximately 6 days later. Peripheral FSH concentrations during the oestrous cycle in control animals displayed a pattern of three waves, each of which closely preceded a wave of follicular development. Concentrations of FSH in GnRHa-treated heifers showed a normal pattern for the first wave after the start of treatment. During the next wave, concentrations increased and remained at the peak values until about 4 days after the end of treatment. An additional ovulation was induced in 11 of 14 GnRHa-treated heifers within 2-3 days of the start of treatment, and a significant (P < 0.05) increase in serum progesterone concentrations was detected 2 days later. All GnRHa-treated heifers then showed a normal follicular wave, with the development and regression of a dominant follicle. The dominant follicles from the next wave grew to only 7-9 mm in diameter and remained at this size until the end of treatment, when they resumed growth, ovulated approximately 7 days later and formed corpora lutea. We conclude that chronic treatment of heifers with GnRHa for 3 weeks suppresses pulsatile secretion of LH and blocks the development of dominant follicles beyond 9 mm in diameter, preventing the preovulatory LH surge and ovulation. However, GnRHa did not suppress the secretion of FSH within the 3 week treatment period. The maintenance of the dominant follicles for an extended period should provide an ideal model to study the control of follicular atresia in cattle in vivo.

Relationship of circulating steroid hormones, luteal luteinizing hormone receptor and progesterone concentration, and embryonic mortality during early embryogenesis in the domestic cat.

Serum hormones, corpus luteum (CL) progesterone, and CL LH receptors were characterized and interrelated to ovarian follicle and CL number and preimplantation embryo quality/survival in the cat. Blood samples were collected from queens ovariohysterectomized at 64 (n = 7), 76 (n = 11), 100 (n = 8), 124 (n = 7), 148 (n = 6), or 480 (n = 8) h after first copulation (3-times-daily matings on Days 2 and 3 of estrus). Ovarian CL were enucleated, weighed, and bisected; one hemi-CL was assayed for progesterone and the other for LH receptors. Serum was assessed for estradiol-17 beta and progesterone. Serum estradiol-17 beta concentrations did not return (p > 0.05) to baseline approximately 20 pg/ml) until 124 h after first copulation, whereas serum progesterone began to increase (> 1 ng/ml) by 76 h, was elevated (p < 0.05) by 124 h, and continued to rise thereafter. Serum progesterone was highly correlated with CL mass and LH receptor and progesterone concentration (range, r = 0.69-0.82; p < 0.01). CL progesterone and LH receptor concentrations were similar (p > 0.05) at 64 and 76 h, and both increased (p < 0.05) at subsequent time intervals and were correlated closely (r = 0.65; p < 0.01). Although ovarian CL were distinct and well organized by 64 h, pronounced elevations in serum progesterone and CL LH receptors and progesterone did not occur until at least 36 h later. The rapid increase in serum progesterone concentrations between 100 and 148 h was related to accelerated LH receptor synthesis and CL progesterone production and not entirely to enhanced CL growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased LH receptor mRNA and extended corpus luteum function induced by prolactin and indomethacin treatment in vivo in hysterectomized pseudopregnant rats.

To assess the effects of prostaglandins and prolactin on corpus luteum function and regression, sterile-mated adult pseudopregnant rats hysterectomized on day 5 after mating were injected with indomethacin or prolactin. Daily samples of blood were collected via the tail, from day 12 to day 21, and assayed for serum concentrations of progesterone, 20 alpha-dihydroprogesterone and LH, whereafter corpora lutea and the remainder of ovaries were separated and the tissue content of PGF2 alpha, PGE2 and LH receptor mRNA were measured. Injections of prolactin (8 iu) s.c. or a low dose of indomethacin (200 micrograms kg-1) s.c. were administered twice a day, beginning on day 13 after mating. Both indomethacin and prolactin significantly increased serum progesterone concentrations (P < 0.05; n = 8), and extended the period of functional corpora lutea when compared with controls. Indomethacin, but not prolactin, lowered the concentration of serum 20 alpha-dihydroprogesterone. In the corpora lutea of indomethacin-treated animals, collected on day 21, both prostaglandins measured were reduced in concentration by 50% or more, compared with controls (P < 0.05; n = 8), whereas prolactin had no effect. Both prolactin and indomethacin treatment caused a substantial (tenfold) increase in the concentration of LH receptor mRNA, confined solely to the luteal compartment. These findings in vivo provide further evidence for a luteolytic role of locally synthesized prostaglandins in the rat ovary. Furthermore, prolactin can sustain corpus luteum function by exerting a luteotrophic effect during the late luteal phase, as judged by the stimulation of progesterone synthesis and the expression of LH receptors.

Endocrinology: Pre-ovulatory progesterone growth rate in patients treated with gonadotrophin-releasing hormone agonist and outcome of in-vitro fertilization

The present study was undertaken to assess whether the increase in serum progesterone concentration following the administration of human chorionic gonadotrophin (HCG) may have predictive value on the in-vitro fertilization (IVF) success rate. Progesterone concentration on the day of HCG administration and the increase in progesterone concentration on the following day were evaluated in 140 consecutive patients undergoing IVF with embryo transfer. Stimulation protocol in all study patients entailed intranasal administration of short-acting gonadotrophin-releasing hormone agonist (GnRHa) buserelin and human menopausal gonadotrophin. A pregnancy rate of 37.2% was achieved when at least three embryos were transferred. The only significant difference between conception and non-conception cycles was found in serum progesterone concentrations after HCG administration (P < 0.01), whereas the mean progesterone concentration on the day of HCG did not differ. No difference in other hormonal or cycle parameters was observed. The increase in progesterone concentration was significantly greater in the group of patients who achieved pregnancy than in the group who did not (2.2 +/- 0.2 versus 1.6 +/- 0.1 ng/ml, respectively; P < 0.01). A critical breakpoint in serum progesterone was arbitrarily determined at 1 ng/ml. An increase in progesterone concentration > or = 1 ng/ml when three or more embryos were transferred was associated with a positive predictive value for pregnancy of 40.4% (sensitivity of 94.7%), whereas a negative predictive value of 86.7% was obtained when this value was < 1 ng/ml. These findings indicate that an adequate rise in serum progesterone following HCG administration provides useful information about the possible outcome of the treated cycle.