Higher Estradiol Concentrations Research Articles

High concentrations of inhibin A and inhibin B in ovarian serous cystadenoma: relationship with oestradiol and nitric oxide metabolites.

Inhibin production has been demonstrated in malignant epithelial ovarian tumours, but secretion of inhibins by benign cystadenoma has not yet been reported. The present study evaluated the concentrations of inhibin A and inhibin B and the relationship with oestradiol and nitric oxide metabolites in fluid collected from benign ovarian serous cystadenomas (n = 15). In addition, follicular fluid samples (n = 14) from women with regular ovulatory cycles undergoing ovarian stimulation for IVF were studied as a reference group. High concentrations of inhibin A (median = 89.3 ng/ml) and inhibin B (median = 116.1 ng/ml) were found in the cystic fluid of ovarian serous cystadenomas. These inhibin concentrations were even higher than in follicular fluid of stimulated follicles (inhibins A and B = 41.2 and 46.8 ng/ml respectively; P: < 0.001), whereas oestradiol was approximately 18-fold lower in cystic fluid than in follicular fluid (median = 34 versus 622 pg/ml, P: < 0.001). In ovarian cysts, the concentrations of inhibin A and oestradiol were inversely correlated (r = -0.678, P: = 0.008). Cystic fluid samples containing the highest concentrations of NO(2)(-)/NO(3)(-) (45-60 micromol/l) had lower inhibin A and higher oestradiol concentrations than those samples containing lower concentrations (10-25 micromol/l) of NO(2)(-)/NO(3)(-). It is concluded that high amounts of dimeric inhibins are present in ovarian serous cystadenoma. The source of inhibins and the determinants of the inverse association of inhibin A with oestradiol and nitric oxide remain to be determined.

The role of LH pulse frequency in ACTH-induced ovarian follicular cysts in heifers

The aim of the present study was to induce ovarian cysts experimentally in cattle using ACTH and to closely examine the role of LH pulse frequency in ovarian cyst formation. Five regularly cycling Holstein–Friesian heifers (15–18-month-old) were used. Ovaries were scanned daily using an ultrasound scanner with a 7.5MHz rectal transducer. Daily blood samples were obtained via tail venepuncture for hormone analyses. Additional blood samples (for FSH and LH pulses) were obtained through an indwelling jugular vein catheters every 15min for 8h on Days 2 (early luteal phase; ELP), 12 (mid-luteal phase; MLP) and 19 (follicular phase; FP) of control estrous cycle and on alternate days during follicular cyst (FC) formation and persistence. Cysts were induced using subcutaneous injections of ACTH (Cortrosyn® Z; 1mg) every 12h for 7 days beginning on Day 15 of the subsequent estrous cycle. Plasma concentrations of progesterone (P4), estradiol-17β, FSH and LH were determined by double antibody radioimmunoassay while cortisol concentration was determined by enzyme immunoassay (EIA). Ovarian follicular and endocrine dynamics were normal during the control estrous cycles. Ovarian follicular cysts were induced in four of the five heifers. Mean maximum size of cysts was larger (P<0.05) than that of ovulatory follicles (26.78±3.65 versus 14.1±0.90mm), respectively. Cortisol levels were increased during ACTH treatment. High concentrations of estradiol and low progesterone were observed after cyst formation. LH pulse frequency was significantly reduced (P<0.05) during cyst formation and persistence compared to ELP (7.5±0.75) and FP (6.5±0.58), but was not significantly (P=0.23) different from MLP (2.8±0.29) pulses. Mean LH pulse amplitude and concentrations were not different. Similarly, the mean pulse frequency, amplitude and concentration of FSH were not different between control study and cystic heifers. These results suggest that the LH pulse frequency observed following ACTH treatment may interact with high estradiol concentration to induce ovarian cyst formation in heifers.

Antiproliferative effects of progesterone antagonists and progesterone receptor modulators on the endometrium

Progesterone antagonists (PAs, antiprogestins) can modulate estrogenic effects in various estrogen-dependent tissues. These modulatory effects are complex and depend on species, tissue, type of compound, dose, and duration of treatment. In non-human primates, PAs, including mifepristone, ZK 137 316 and ZK 230 211, inhibit endometrial proliferation and induce amenorrhea. When administered chronically at relatively low doses, these compounds block the mitotic activity of endometrial epithelium and induce stromal compaction in a dose-dependent manner in both spayed and intact monkeys at high estradiol concentrations. These effects were accompanied by an atrophy of spiral arteries. The antiproliferative effects were endometrium-specific, since the estrogenic effects in the oviduct and vagina were not inhibited by PAs. Similar endometrial antiproliferative effects were also found after treatment with the progesterone receptor modulator (PRM), mesoprogestin J1042. The endometrial antiproliferative effects of PAs, particularly within the endometrial glands, were also observed in spayed rabbits. In spayed rats, however, the PAs did not inhibit, but rather enhanced, various estrogen responses, including endometrial proliferation, pointing to species-specific differences. In conclusion, our studies indicate that both pure PAs and PRMs selectively inhibit estrogen-dependent endometrial proliferation in the primate endometrium without affecting estrogenic response in other estrogen-dependent tissues or inducing unscheduled bleeding. Our studies indicate that the spiral arteries, which are unique to the primate endometrium, are the primary targets that are damaged or inhibited by PAs and PRMs. The damage to these unique vessels may underlay the paradoxical, endometrium-specific, antiproliferative effects of these compounds. Hence, the properties of PAs and PRMs (mesoprogestins) open up new applications in gynecological therapy and hormone replacement therapy.

Studies of the oestrous cycle, oestrus and pregnancy in the koala (Phascolarctos cinereus).

As an integral part of the development of an artificial insemination programme in the captive koala, female reproductive physiology and behaviour were studied. The oestrous cycle in non-mated and mated koalas was characterized by means of behavioural oestrus, morphology of external genitalia and changes in the peripheral plasma concentrations of oestradiol and progestogen. The mean (+/- SEM) duration of the non-mated oestrous cycle and duration of oestrus in 12 koalas was 32.9 +/- 1.1 (n = 22) and 10.3 +/- 0.9 (n = 24) days, respectively. Although the commencement of oestrous behaviour was associated with increasing or high concentrations of oestradiol, there were no consistent changes in the morphology or appearance of the clitoris, pericloacal region, pouch or mammary teats that could be used to characterize the non-mated cycle. As progestogen concentrations remained at basal values throughout the interoestrous period, non-mated cycles were considered non-luteal and presumed anovulatory. After mating of the 12 koalas, six females gave birth with a mean (+/- SEM) gestation of 34.8 +/- 0.3 days, whereas the remaining six non-parturient females returned to oestrus 49.5 +/- 1. 0 days later. After mating, oestrous behaviour ceased and the progestogen profile showed a significant increase in both pregnant and non-parturient females, indicating that a luteal phase had been induced by the physical act of mating. Progestogen concentrations throughout the luteal phase of the pregnant females were significantly higher than those of non-parturient females. Parturition was associated with a decreasing concentration of progestogen, which was increased above that of basal concentrations until 7 days post partum.

Studies of the oestrous cycle, oestrus and pregnancy in the koala (Phascolarctos cinereus)

As an integral part of the development of an artificial insemination programme in the captive koala, female reproductive physiology and behaviour were studied. The oestrous cycle in non-mated and mated koalas was characterized by means of behavioural oestrus, morphology of external genitalia and changes in the peripheral plasma concentrations of oestradiol and progestogen. The mean (+/- SEM) duration of the non-mated oestrous cycle and duration of oestrus in 12 koalas was 32.9 +/- 1.1 (n = 22) and 10.3 +/- 0.9 (n = 24) days, respectively. Although the commencement of oestrous behaviour was associated with increasing or high concentrations of oestradiol, there were no consistent changes in the morphology or appearance of the clitoris, pericloacal region, pouch or mammary teats that could be used to characterize the non-mated cycle. As progestogen concentrations remained at basal values throughout the interoestrous period, non-mated cycles were considered non-luteal and presumed anovulatory. After mating of the 12 koalas, six females gave birth with a mean (+/- SEM) gestation of 34.8 +/- 0.3 days, whereas the remaining six non-parturient females returned to oestrus 49.5 +/- 1. 0 days later. After mating, oestrous behaviour ceased and the progestogen profile showed a significant increase in both pregnant and non-parturient females, indicating that a luteal phase had been induced by the physical act of mating. Progestogen concentrations throughout the luteal phase of the pregnant females were significantly higher than those of non-parturient females. Parturition was associated with a decreasing concentration of progestogen, which was increased above that of basal concentrations until 7 days post partum.

Higher estradiol concentrations are associated with elevated lipids in men with coronary artery disease

Higher estradiol concentrations are associated with elevated lipids in men with coronary artery disease

Response to activated protein C during normal menstrual cycle and ovarian stimulation.

Oestrogen has been pointed out as a pre-thrombotic factor. Protein C is a key enzyme in the down-regulation of blood coagulation. Recent data suggest that activated protein C (APC) resistance which is not due to the factor V:Q 506 Leiden mutation and appears to be acquired, is also a risk factor for thrombosis. In this study, we evaluated the endogenous oestradiol production and its possible influence on APC. Eighteen normally menstruating women were studied during one ovulatory cycle. Furthermore, 20 women undergoing controlled ovarian stimulation, and achieving extremely high oestradiol concentrations, were investigated. Normalized APC (nAPC) ratio (clotting time of tested sample/clotting time of pooled control plasma) was measured. Samples collected on menstrual cycle days 1-3, 6-8, 13-14, 20-24 corresponded to nAPC ratios 1.02 +/- 0.19 (mean +/- SD), 1.05 +/- 0. 15, 1.02 +/- 0.16 and 1.03 +/- 0.21 respectively. During ovarian stimulation, the nAPC ratios were 0.99 +/- 0.12, 1.03 +/- 0.18, 1.01 +/- 0.16 and 0.97 +/- 0.13 at oestradiol minimum, days 5-8 pre-oocyte retrieval, oestradiol maximum and at oocyte retrieval respectively. In spite of the great difference in the concentrations of oestradiol between women in normal menstrual cycle and women undergoing ovarian stimulation, no difference in nAPC ratios was observed.

Regulation of cell growth and HPV genes by exogenous estrogen in cervical cancer cells.

Human papillomavirus (HPV) infection is known as the major cause of the development of cervical cancer. The E6 and E7 proteins of oncogenic HPV can play critical roles in immortalization and malignant transformation of cervical epithelial cells. From the previous epidemiologic data, it has been determined that long-term use of oral contraceptives may be a risk factor for cervical cancer. Investigation of the estrogenic and antiestrogenic effects on the proliferation of cervical cancer cells and the gene expression of HPV would help to explain the role of estrogen in the HPV-associated pathogenesis of cervical cancer. In this study, cervical cancer cells (HeLa, CaSki, and C33A) were cultured in vitro in the presence of 17beta-estradiol or tamoxifen to observe their regulatory growth effect and HPV E6/E7 gene expression. The estrogenic effect on the promoter activity of HPV URR was further confirmed by transient transfection assay, which was conducted in C33A cells using the HPV-18 URR-CAT reporter plasmid. The supplemental effect of estrogen receptors on URR promoter activity was also evaluated. The proliferation of HeLa and CaSki cells was stimulated by estradiol at physiologic concentration levels (</=1 x 10-6 M). At a low concentration (0.1 x 10-6 M), tamoxifen also stimulated the proliferation of HeLa and CaSki cells. In contrast to HPV-positive cervical cells, the proliferation of C33A was not influenced by exogenous estradiol or tamoxifen, indicating that HPV might play a role in the hormonal stimulation of cell growth. Interestingly, the proliferation of HeLa was markedly suppressed at high concentrations of estradiol and tamoxifen (5 and 10 x 10-6 M). The levels of HPV-18 E6 and E7 mRNA were significantly increased by estradiol at a concentration of 0.5 x 10-6 M. Transient transfection experiments using the HPV URR-CAT reporter plasmid in C33A cells indicated that the expression of HPV E6/E7 genes was increased by the treatment of estradiol and tamoxifen. Co-transfection of estrogen receptors (ER) and URR-CAT leads to a fourfold increase in CAT activity by estradiol or tamoxifen at physiologic concentrations. When estradiol or tamoxifen was administered at high concentrations (5 x 10-6 M), a DNA ladder, typically indicative of apoptosis, was observed in HeLa cells. In conclusion, estradiol stimulated the growth of HPV-positive cervical cancer cells, as did tamoxifen at low concentrations (0.1 x 10-6 M). The growth stimulation of HPV-positive cervical cancer cells by estrogen appeared to be related to the increased expression of HPV E6/E7. Growth suppression observed at high concentrations of estradiol and tamoxifen in HeLa cells might be a result of apoptosis. Taken together, these data suggested that exogenous estradiol might be a risk factor in HPV-mediated cervical carcinogenesis.

High serum oestradiol concentrations in fresh IVF cycles do not impair implantation and pregnancy rates in subsequent frozen-thawed embryo transfer cycles.

High oestradiol concentrations may be detrimental to the success of in-vitro fertilization (IVF) treatment. A total of 1122 women aged <40 years who were undergoing their first IVF cycle were evaluated retrospectively. Serum oestradiol concentrations on the day of human chorionic gonadotrophin (HCG) administration were categorized into three groups: group A <10 000 pmol/l; group B 10 000-20 000 pmol/l and group C >20 000 pmol/l. In fresh cycles, group A had significantly lower pregnancy rates per transfer (16.2 versus 23.7% respectively, P = 0.005, chi(2)) and implantation rates (8.7 versus 11.7% respectively, P = 0.037, chi(2)), when compared with group B. The pregnancy rate per transfer in group C was significantly lower than that in group B (12.1 versus 23.7%, P = 0.049, chi(2)) and group C had the lowest implantation rate (6.4%). In frozen-thawed embryo transfer cycles, implantation rates in groups A, B and C were similar (7.5, 8.1 and 9.6% respectively) and the pregnancy rates were also comparable in all groups. In conclusion, high serum oestradiol concentrations in fresh IVF cycles may adversely affect implantation and pregnancy rates. Embryo quality seemed unaffected as excess embryos from different groups had similar implantation and pregnancy rates in frozen-thawed embryo transfer cycles. The reduced implantation was probably due to an adverse endometrial environment resulting from high serum oestradiol concentrations.

Estrogen metabolism as a regulator of estrogen action in the mammary gland.

Estrogen action in the target cells is dependent on estrogen receptor activity and intracellular estrogen concentration, which, in turn, is affected by the serum concentration and local metabolism in these cells. During the reproductive years the main source of estrogens is the ovarian follicles, but in postmenopausal women most of the estrogens are formed in peripheral tissues. 17Beta-hydroxysteroid dehydrogenases (17HSDs) catalyze the reaction between 17beta-hydroxysteroids and 17-ketosteroids, and several distinct 17HSD isoenzymes have been characterized. 17HSD type 1 catalyzes the reaction from low-activity estrone to high-activity estradiol. The type 2 enzyme has an opposite activity, thereby reducing the exposure of tissues to estrogen action. 17HSD type 1 is expressed both in steroidogenic tissues and in the target tissues of steroid action, such as normal and malignant breast tissue, where it may be responsible for maintaining the high intracellular estradiol concentration seen in breast cancer specimens. Therefore, 17HSD type 1 inhibitors may be useful in the treatment and/or prevention of estrogen-dependent malignancies, such as breast cancer. This article deals mainly with 17HSD types 1 and 2 and their role in estrogen action in breast tissue.

Epidermal Growth Factor and 17ß-Estradiol Effects on Proliferation of a Human Gastric Cancer Cell Line (AGS)

Background

Ovarian stimulation and endometrial receptivity.

Endometrial receptivity is a limiting step in the success of in-vitro fertilization (IVF). To investigate this issue, we selected a specific population of high responder patients in whom implantation was impaired, even when good quality embryos were transferred. We present a series of studies showing that high oestradiol concentrations on the day of human chorionic gonadotrophin (HCG) administration are detrimental to uterine receptivity. In addition, we suggest clinical strategies to improve endometrial receptivity in high responder patients using a step-down regimen.

Effect of estradiol and exercise on lymphocyte proliferation responses in female mice

Many North American women are encouraged to take estrogen replacement therapy and to begin (or continue) physical activity during the postmenopausal years. This study investigated the effect of estradiol exposure and physical exercise on lymphocyte proliferation responses to T and B cell mitogens in female mice. Sixty C57BL/6 mice were randomized to hormone and exercise treatment conditions: hormone treatment consisted of estradiol in vivo (71.4 μg estradiol per day for 21 days) or placebo pellet following bilateral ovariectomy, or surgical sham (mice were not ovariectomized). Exercise consisted of a single forced treadmill run (26 m/min, 6° slope, 90 min) or a sedentary control condition. Outcomes were thymic and splenic lymphocyte proliferation responses to the mitogens concanavalin A (ConA, 1.0 and 5.0 μg/mL concentrations) and lipopolysaccharide (LPS, 0.5, 1.0, and 2.0 μg/mL concentrations). In the thymus, there was a significant reduction of proliferation to ConA in the Ovx + E2 animals relative to the other conditions at both concentrations of mitogen. At 1.0 μg/mL concentration, there was a significant interaction of hormone and exercise treatments. Sham (control) mice given exercise had a higher proliferation response relative to sedentary counterparts, whereas E2 mice did not differ in proliferation responses, irrespective of exercise condition. In the spleen, exposure to high concentrations of estradiol was associated with reduced proliferation responses to both mitogens; there were, however, no main or interaction effects of exercise. These results suggest that high levels of estradiol exposure following ovariectomy in mice significantly reduces lymphocyte blastogenesis responses, and that thymic immunomodulation after acute exercise is masked by the hormonal effect.

Postpartum thyroid diseases through the ages: a historical view.

ThyroidVol. 9, No. 7 Postpartum Thyroid Diseases Through The Ages: A Historical ViewROBERT C. SMALLRIDGEROBERT C. SMALLRIDGESearch for more papers by this authorPublished Online:30 Jan 2009https://doi.org/10.1089/thy.1999.9.671AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited byPostpartum Thyroid DysfunctionThyroid and Parathyroid Diseases in PregnancyThyroid disorders in pregnancy25 September 2012 | Nature Reviews Endocrinology, Vol. 8, No. 11Postpartum and Silent Thyroiditis14 May 2012Thyroid and Parathyroid Diseases in PregnancyThyroid and Parathyroid Diseases in PregnancyEffect of High Concentration of Estradiol on Thyroid Specific Genes Expression and Cell GrowthJournal of Korean Endocrine Society, Vol. 21, No. 1Thyroiditis, PostpartumHypothyroidism and PregnancyThe Endocrinologist, Vol. 12, No. 5RECOGNIZING, UNDERSTANDING, AND TREATING POSTPARTUM THYROIDITISEndocrinology and Metabolism Clinics of North America, Vol. 29, No. 2 Volume 9Issue 7Jul 1999 To cite this article:ROBERT C. SMALLRIDGE.Postpartum Thyroid Diseases Through The Ages: A Historical View.Thyroid.Jul 1999.671-673.http://doi.org/10.1089/thy.1999.9.671Published in Volume: 9 Issue 7: January 30, 2009PDF download

Serum oestradiol and breast cancer risk.

Breast cancer risk is increased by early menarche and late menopause, suggesting that the long duration of exposure of the breasts to the high levels of ovarian steroids in premenopausal women increases risk. Recent prospective studies have shown that postmenopausal women who develop breast cancer have significantly greater prediagnostic serum concentrations of oestradiol than postmenopausal women who remain healthy. Estimation of long-term oestradiol concentrations in premenopausal women is difficult, and few data are available from prospective studies, but these are compatible with the hypothesis that relatively high oestradiol concentrations in premenopausal women are also associated with an increase in breast cancer risk. Women in populations with low breast cancer rates have low serum oestradiol concentrations both before and after the menopause. The serum concentration of oestradiol is probably a major determinant of breast cancer risk, but more data are needed to confirm this and to investigate the possible roles of other sex hormones.

Aromatase within the breast.

In situ aromatization and enhanced uptake of estradiol from plasma are two potential mechanisms for maintenance of high concentrations of estradiol found in breast tumors of postmenopausal patients. To test the relative importance of these two mechanisms, a nude mouse model was established by inoculating aromatase (A+) and/or sham (A-) transfected MCF-7 cells into ovariectomized mice. Postmenopausal hormonal status was simulated by providing estradiol Silastic implants which clamped plasma estradiol levels at 5-20 pg/ml. We demonstrated that in situ aromatization rather than the uptake mechanism is the key determinant of tumor estradiol levels and tumor growth rate under conditions reflecting the postmenopausal state. The importance of intratumoral aromatase was also suggested by the findings that long-term estrogen deprivation increases sensitivity to estradiol and enhances aromatase activity in MCF-7 cells. The results of our in vivo and in vitro studies suggest that complete blockade of in situ aromatization in the breast would provide added benefit to postmenopausal breast cancer patients, especially those who relapse from antiestrogen therapy.

Effect of obesity on estradiol level, and its relationship to leptin, bone maturation, and bone mineral density in children.

The purpose of this study was to investigate 24-h estradiol and leptin levels in obese and nonobese children to further understand the roles of estradiol and leptin in obesity and puberty. We measured serum estradiol, leptin, insulin, glucose, and GH levels every hour for 24 h in 18 obese (12 females and 6 males) and 30 nonobese (11 females and 19 males) prepubertal and early pubertal (stages 1-2) children. Bone age and dual energy x-ray absortiometry (DEXA) were obtained upon completion of the 24-h study. Obese children were significantly younger than nonobese children, with no difference in pubertal stage, height, or bone age between the 2 groups. Obese children had greater bone age to chronological age ratios than nonobese children, indicating a more advanced rate of bone maturation. Mean 24-h estradiol levels correlated significantly with chronological age and bone age as well as with insulin-like growth factor I, insulin-like growth factor-binding protein-3, dehydroepiandrosterone sulfate, mean 24-h GH, and lean body mass. Mean 24-h estradiol levels did not differ between obese and nonobese children [1.65+/-1.47 us. 2.75+/-3.30 pmol/L (0.45+/-0.40 vs. 0.75+/-0.90 pg/mL), respectively]. Similar mean 24-h estradiol levels in obese and nonobese children are consistent with the increased bone maturation of the obese children. Estradiol did not correlate significantly with DEXA fat mass, body mass index, or arm fat measures of adiposity. Obese children had higher 24-h mean leptin concentrations than nonobese children (28.6+/-17.4 vs. 6.8+/-7.1 ng/mL; P < 0.001). Leptin concentrations positively correlated with DEXA fat mass, body mass index, and arm fat measurement of adiposity. Girls had higher 24-h mean leptin levels than boys when controlling for adiposity. Estradiol and leptin concentrations fluctuated over a 24-h period in both groups, with all children having higher leptin concentrations at night and higher estradiol concentrations in the morning. This diurnal rhythm was of a similar pattern, but at higher levels for leptin and lower levels for estradiol in the obese children compared to nonobese children. There was no significant correlation between estradiol and leptin levels. Bone mineral density, as measured by DEXA, did not differ between obese and nonobese children. Similar bone mineral density values in obese and nonobese children are consistent with the increased bone maturation of the obese children. Bone mineral density was not correlated with estradiol or leptin level in these children. In conclusion, obese children had similar estradiol levels and equivalent bone ages at a younger chronological age than nonobese children. Leptin was higher in these obese children, but did not correlate with estradiol level or bone age. These findings suggest that the role of leptin in both obesity and pubertal development is not directly correlated with the estradiol level.

Inhibition by oestradiol of oxidative stress-induced apoptosis in pig ovarian tissues.

Oxidative stress-induced apoptotic cell death has been implicated in the mechanisms of corpus luteum regression and follicular atresia. The objective of this investigation was to determine whether the antioxidant, oestradiol influenced apoptosis in pig luteal and follicular tissues exposed in vitro to hydrogen peroxide. Immunolocalization of fragmented DNA (a biochemical marker of apoptosis) in large steroidogenic luteal and granulosa cells was inhibited by oestradiol. Protection against apoptosis required relatively high concentrations of oestradiol (> or = 40 pg ml-1 incubation media) and was largely unmitigated by actinomycin D (suggesting a predominantly receptor-independent nongenomic mode of action). Ovarian cells were not protected by other (nonaromatizable) steroid hormones. It is suggested that oestradiol functions at the ovary as a reactive oxygen scavenger during pregnancy-mediated luteal rescue and folliculogenesis.

Steady-state concentrations of mRNA encoding two inhibitors of protein kinase C in ovine luteal tissue.

Prostaglandin F2 alpha (PGF2 alpha) decreases secretion of progesterone from the corpus luteum in domestic ruminants. However, it is less effective during the early part of the oestrous cycle (Louis et al., 1973) and at the time of maternal recognition of pregnancy (Silvia and Niswender, 1984; Lacroix and Kann, 1986). Decreased luteal responsiveness may be due to failure of PGF2 alpha to activate fully its normal second messenger system, protein kinase C (PKC). Alternatively, increased resistance of the corpus luteum to PGF2 alpha might be attributable to greater concentrations of recently identified biological inhibitors of PKC. These possibilities were addressed by measuring steady-state concentrations of mRNA encoding PGF2 alpha receptor and two inhibitors of PKC, protein kinase C inhibitor-1 (PKCI-1) and kinase C inhibitor protein-1 (KCIP-1, brain 14-3-3 protein), in corpora lutea collected from ewes on days 4, 10 and 15 of the oestrous cycle (n = 5 per day) and day 15 of pregnancy (n = 7). There were no differences in mean concentrations of mRNA encoding PGF2 alpha receptor among the groups. However, concentrations of mRNA encoding both inhibitors of PKC were higher (P < 0.01) on day 4 of the oestrous cycle compared with the other groups. Treatment of ewes with a luteolytic dose of PGF2 alpha, which activates PKC, did not change concentrations of mRNA encoding either PKCI-1 or KCIP-I up to 24 h later. Luteal expression of mRNA encoding the PKC inhibitors and PGF2 alpha receptor was also examined in ewes treated with oestradiol in vivo for 16 h in the midluteal phase. High concentrations of oestradiol in serum (20 and 70 pg ml-1) did not influence quantities of any of the mRNAs examined. Therefore, an increase in PKC inhibitors may be involved in resistance of the corpus luteum to PGF2 alpha during the early part of the oestrous cycle but does not appear to mediate the increased resistance of the corpus luteum to PGF2 alpha during maternal recognition of pregnancy. Neither PGF2 alpha nor oestradiol affected steady-state concentrations of mRNAs encoding PKCI-1 or KCIP-I.

Sex and species differences in cell-mediated immune responses in voles

Males generally display reduced immune responses and greater susceptibility to disease than females, possibly reflecting the suppressive effects of androgens on the immune system. It is presumed that this androgenic effect on immune function is more pronounced among polygynous than monogamous species because concentrations of circulating androgens are generally higher among polygynous than monogamous males. The present study examined sex and species differences in cell-mediated immunity of two Microtus species. Cell-mediated immunity was assessed among individually housed polygynous meadow voles (M. pennsylvanicus) and monogamous prairie voles (M. ochrogaster) by examining the proliferative responses of splenocytes to the T-cell mitogen concanavalin A (Con A) and the B-cell mitogen lipopolysaccharide (LPS). Neither sex nor species differences were observed in response to stimulation with Con A. In contrast, meadow voles exhibited higher proliferative responses to LPS than prairie voles. Sex differences in immune function were only observed among prairie voles; males exhibited higher proliferative responses to LPS than females. Male meadow voles had higher circulating testosterone concentrations than male prairie voles and female prairie voles had higher estradiol concentrations than female meadow voles. Males of both Microtus species weighed more than conspecific females. The immunological differences were not related to differences in either body mass or hormone concentrations. Overall, these data do not support the hypothesis that higher androgen concentrations in polygynous males influence sex or species differences in immune function.