Higher FSH Concentrations Research Articles

Reintroducing serum FSH measurement during ovarian stimulation for ART

Research questionWhat is the impact of systemic FSH concentrations during ovarian stimulation for IVF/intracytoplasmic sperm injection on systemic progesterone concentrations in the late follicular phase? DesignPost-hoc analysis of a previously performed randomized controlled trial (RCT) performed between November 2017 and February 2020 in a tertiary IVF centre. The RCT included patients with infertility undergoing ovarian stimulation in a gonadotrophin-releasing hormone (GnRH) antagonist protocol. The GnRH antagonist was administered at 08:00 h and recombinant FSH at 20:00 h. Ultrasound and blood tests were performed 3–5 h after the GnRH antagonist. ResultsThe subgroup analysis comprised 105 patients. Systemic FSH concentrations increased from Day 2/3 until initiation of GnRH antagonist and remained constant until the day of trigger (DoT). The total group was split according to the median FSH DoT concentration (12.95 IU/l; Group A <12.95 IU/l; Group B ≥12.95 IU/l). Significant differences, with the higher concentrations in Group B, were found for: systemic FSH concentration on Day 2/3 (P = 0.04), total gonadotrophin dosage (P = 0.03), progesterone on DoT (P = 0.001) and progesterone per follicle (P = 0.004). In the total group, systemic DoT FSH concentration was statistically significantly positively correlated with the DoT progesterone concentration and the ratio of progesterone per follicle (ρ = 0.37 and 0.38, respectively, both P < 0.001). No significant correlations were seen between the systemic DoT FSH concentration and the number of retrieved oocytes. ConclusionWhile ovarian response seems to be independent from the systemic FSH concentrations on the DoT, high concentrations of circulatory FSH augment the production of progesterone.

Effect of supra-nutritional selenium-enriched probiotics on hematobiochemical, hormonal, andDoppler hemodynamic changes in male goats.

In this study, the influence of supra-nutritional organic selenium (Se) supplement on hematology and plasma biochemicals, including antioxidant parameters and plasma reproductive hormones, as well as blood flow characteristics in the supratesticular and common carotid arteries (STA and CCA, respectively) were investigated. For this purpose, 15 male goats were used and classified into three equal groups according to the supplementation of the basal diet (BD): negative control (NC), probiotic (Pro), and Se-probiotic (Se-Pro) groups. Blood perfusion in the STA and CCA was assessed by Doppler ultrasonography at three different time intervals: at the experimental onset (T0), 3weeks of dietary supplement (T3), and after 6weeks of observation (T6). Concomitantly, blood samples were withdrawn for hematobiochemical and hormonal changes. Results revealed no evidence of clinical abnormality, with some enhanced hematological parameters and antioxidant (SOD and GPX) levels in goats of the Se-Pro and Pro groups. High concentrations of FSH were found in the Se-Pro at T6 compared to its values in other groups. Similarly, testosterone levels were elevated in the Pro and Se-Pro groups at T3 compared to other time points. There were significant increases in levels of IGF-1 in the Pro and Se-Pro groups compared to the NC group. Significant (P < 0.05) increases in the values of the blood volume within the CCA and the STA were noted in the Se-Pro group, and the highest values were observed at T6 (CCA, 427.4 ± 33ml/min; STA, 49.9 ± 5.0ml/min). In conclusion, supra-nutritional organic selenium improves some hematobiochemical parameters, reproductive hormones, and the blood perfusion within the CCA and STA in goats.

190 Effect of TCM-199 and synthetic oviductal fluid medium supplemented with varying hormone concentrations on invitro maturation of canine oocytes

Invitro oocyte maturation (IVM) in the domestic canine is yet to be optimized, with low rates of cumulus-oocyte complexes (COCs) reaching MII. This limits the progression of assisted reproductive technologies, which could benefit breeding programs for assistance dogs and endangered Canidae. Canine oocyte maturation differs from that in other mammals, with the ovulation of a COC in the germinal vesicle stage and nuclear maturation occurring in the oviduct. Because of this, the environment in which a canine COC matures is unlike that of other mammals, meaning that IVM protocols cannot be readily adapted. The aim of the current work was to determine (1) the effects of varying concentrations of FSH, human chorionic gonadotrophin (hCG), and oestradiol (E2) during IVM on meiotic resumption and nuclear maturation of canine COCs; and (2) the optimal medium base, either synthetic oviductal fluid (SOF) or tissue culture medium-199 (TCM). Reproductive tracts of bitches (6 months to 7 years of age) were collected from veterinary clinics within 2h of routine spaying. Ovaries were sliced using a scalpel blade, releasing the COCs into aspiration medium. The COCs were randomly allocated to a maturation medium consisting of one of the hormones at two concentrations (FSH: 5 or 10µgmL−1; hCG: 5 or 10IUmL−1; E2: 1 or 5µgmL−1) and for both SOF and TCM base. Each hormone was tested individually for a replicate of eight animals per hormone (total of 12 experimental groups; 24 animals). The COCs were cultured for 72h in their allocated medium and then denuded and stained with Hoechst 33258. Fluorescence microscopy was used to determine nuclear maturation stage. Nuclear maturation rates to MII were analysed using a general linear model with pairwise comparison (SPSS version 25; SPSS Inc./IBM Corp.) with each individual animal acting as a replicate. Canine COCs matured in a SOF-based media had higher rates of meiotic resumption (MI and MII) (SOF: 38.68%, n=515; TCM: 25.78%, n=542; P&amp;lt;0.05) and number reaching MII (SOF: 7.54%; TCM: 4.39%; P&amp;lt;0.05) compared with TCM-based medium. Resumption of meiosis and nuclear maturation to MII did not differ between media with differing E2 or hCG concentrations. The use of FSH at 10µgmL−1 in SOF medium decreased resumption of meiosis (8.57%) and MII rates (0%) compared with 5µgmL−1 FSH in SOF (29.41% and 3.92%, respectively; P&amp;lt;0.05). In summary, our data indicated that higher concentrations of FSH during IVM have a negative effect on meiotic resumption and maturation to MII, whereas canine COCs resume meiosis and mature to MII in higher rates in a SOF-based medium compared with a TCM base. An IVM medium that replicates the invivo environment in which canine COCs mature is beneficial. However, rates of IVM canine oocytes reaching maturity are low, signifying that future research must investigate a greater range of hormone concentrations and combinations to better mimic invivo conditions to assess the possible benefits for canine IVM.

Immunological manipulation of ovulation rate for twinning in cattle

Unlike in sheep, in which immunization against androstenedione causes mild and reasonably controlled increased ovulation rate, in similar studies cattle showed highly variable responses ranging from increased ovulation rate and fertility through to anovulation/anoestrous or superovulation. As a consequence, interest in manipulation of ovulation rate through this approach has declined and is now focused on immunological manipulation of endogenous inhibin following successful studies in sheep. Studies have concentrated on developing a prototype inhibin-based vaccine to be used for twinning in the Australian beef industry. The prototype vaccine (with recombinant ovine inhibin-alpha.3 fusion protein and Montanide:Marcol adjuvant) has proved to be very potent and control of the degree of ovarian stimulation has not been possible. The proportion of cattle with increased ovulation rate after inhibin immunization is affected by timing of booster vaccination within the ovarian cycle, time after vaccination, vaccine formulation and possibly genotype. Physiological studies show that cattle responding to the inhibin vaccine have increased plasma inhibin binding of native bovine inhibin, high plasma FSH concentrations, greater numbers of large (> or = 8 mm) follicles and fewer small (< 5 mm) follicles during the preovulatory wave of follicular development compared with control or non-responding animals. Significant correlations among the response parameters (i.e. inhibin binding, plasma FSH concentrations, number of large follicles and ovulation rate) have been demonstrated. The results indicate that greater understanding of the various processes of folliculogenesis will be necessary to achieve a controlled increase in ovulation rate in cattle.

Aqueous root extract of Chrysophyllum albidum caused dose and duration dependent increases in some reproductive hormones and spermatogenic arrest in the testes of male Wistar rats

Background aimIn ethnomedicine, different parts of Chrysophyllum albidum have been used as herbal remedies for the treatment and management of various ailments. This study was carried out to determine the dose and duration dependent effects of administration of aqueous root extracts of Chrysophyllum albidum on the serum concentrations of some reproductive hormones and testes of the experimental rats.MethodsForty-five adult male Wistar rats were used for this study. They were randomized into 3 groups (groups 1, 2 & 3) of 15 rats each, with each group further randomized into 3 subgroups (subgroups 1a, 1b, 1c; 2a, 2b, 2c; 3a, 3b, 3c) of 5 rats each, according to the dose and duration of extract administration.ResultsAt the 8th week of extract administration, there were significantly (P < 0.05) higher concentrations of FSH in the treated subgroups while at weeks 6 and 8, there were significant (p < 0.05) increases in the serum concentrations of LH of the treated subgroups as compared to those of the control subgroups. Also, at weeks 6 and 8, administration of the extract resulted in significant (P < 0.05) increases in the concentrations of serum testosterone in the treated subgroups. Photomicrograph of the testes revealed focal spermatogenic arrest in the area biopsied in the treated subgroups (with low and high doses) at weeks 6 and 8 of extract administration.ConclusionThe administration of aqueous root extract of Chrysophyllum albidum to male Wistar rats at increasing doses and time duration may affect their fertility and calls for caution in the prolonged use of the plant in folk medicine.

Gonadotrophic pituitary incidentaloma as the cause premature ovarian insufficiency

Objective: evaluate clinical significance pituitary incidentalomas, apparently derived from gonadotropocytes.&#x0D; Design: follow-up study. Patients. Three observations of pituitary microadenomas in patients whose cause for treatment was prolonged amenorrhea. Diagnosed uterine hypoplasia, decreased ovarian reserve, decreased bone mass. Patients combined expressed psycho-emotional symptoms (depression, neuroticism up to mental disorders in one case). The diagnosis of a gonadotrophic incidentaloma is suspected after exclusion of clinical and laboratory signs of prolactinoma, somatotrophic, corticotrophic and thyrotrophic adenoma.&#x0D; Results. In two cases, the clinical picture of severe estrogenic failure was combined with high concentrations FSH, LH and low concentrations of anti-mullerian hormone (AMH). The increase in gonadotrophines, obviously, was both a reaction to a decreased production of estrogens, and the result of their hypersecretion by adenoma. In the observed cases there was no development of ovarian cysts, characteristic for patients with gonadotrophic adenomas, which can be explained by a reduced ovarian reserve. In the third case marked initially normal secretion of FSH and LH, not corresponding to a low concentration of sex steroids. Further there was a complete cessation of the secretion of FSH and LH with a simultaneous rapid decrease in the secretion of AMH. Given the small size of adenomas, in all cases selection of tactics for dynamic observation. All patients were prescribed hormone replacement therapy.&#x0D; Conclusion. For patients with premature ovarian failure, it is advisable to carry out MRI with contrast enhancement to exclude pituitary adenoma.

A novel action of follicle-stimulating hormone in the ovary promotes estradiol production without inducing excessive follicular growth before puberty

In cyclic females, FSH stimulates ovarian estradiol (E2) production and follicular growth up to the terminal stage. A transient elevation in circulating FSH and E2 levels occurs shortly after birth. But what could be the action of FSH on the ovary during this period, and in particular how it stimulates ovarian steroidogenesis without supporting terminal follicular maturation is intriguing. By experimentally manipulating FSH levels, we demonstrate in mice that the mid-infantile elevation in FSH is mandatory for E2 production by the immature ovary, but that it does not stimulate follicle growth. Importantly, FSH increases aromatase expression to stimulate E2 synthesis, however it becomes unable to induce cyclin D2, a major driver of granulosa cell proliferation. Besides, although FSH prematurely induces luteinizing hormone (LH) receptor expression in granulosa cells, LH pathway is not functional in these cells to induce their terminal differentiation. In line with these results, supplying infantile mice with a superovulation regimen exacerbates E2 production, but it does not stimulate the growth of follicles and it does not induce ovulation. Overall, our findings unveil a regulation whereby high postnatal FSH concentrations ensure the supply of E2 required for programming adult reproductive function without inducing follicular maturation before puberty.

Sex- and seasonally related changes in plasma gonadotropins and sex steroids concentration in the European beaver (Castor fiber)

The European beaver (Castor fiber) is the largest free-living rodent in Eurasia which belongs to the group of long-day breeders. A seasonally changing photoperiod may be related to cyclic changes in the secretion of gonadotropins and sex steroids. The goal of our study was to determine sex- and seasonally dependent changes in the concentration of gonadotropins (LH—luteinizing hormone and FSH—follicle-stimulating hormone) and steroids (T—testosterone, E2—estradiol, and P4—progesterone) in the blood plasma of free-living male and female beavers. Blood samples were collected in April—pregnancy in females; July—the end of lactation, raising of offspring; and November—sexual silence. Our results indicate that in females, a higher FSH concentration was noted in July and November than in April. Plasma T content did not differ between males and females, but in females, it was higher in April as compared with July or November. Plasma P4 concentration was the highest in females in April. In summary, our findings indicate, for the first time, that in the European beaver occur sex- and/or seasonally related changes in the concentration of plasma FSH and sex steroids (T and P4). Seasonal differences in the tested hormones can be associated with the differential activity of the hypothalamo-pituitary-gonadal axis during various reproductive stages of the beaver.

Intercycle variability of the ovarian response in patients undergoing repeated stimulation with corifollitropin alfa in a gonadotropin-releasing hormone antagonist protocol

To determine whether individual subject variation in ovarian response between repeated cycles with the same ovarian stimulation protocol can be predicted. Retrospective data analysis. Multicenter, open-label, uncontrolled clinical trial. Women aged 18-39 from a phase 3, open-label, uncontrolled trial with complete data across all cycles (n = 176). Up to three cycles of a single injection of 150 μg corifollitropin alfa for 7 days, then daily recombinant FSH/hMG until three follicles reached ≥17 mm. Gonadotropin-releasing hormone antagonist from stimulation day 5 until day of hCG administration. Numbers of follicles ≥11 mm on day of hCG in cycles 1-3, transition in ovarian response type between cycles from low (0-<6), normal (6-<18), and high (≥18), and serum FSH concentrations and antral follicle count (AFC) at each cycle start. The mean (SD) numbers of follicles ≥11 mm on day of hCG were 13.4 (6.2), 13.3 (5.4), and 13.8 (6.4) in cycles 1, 2 and 3, respectively. Between cycles 1 and 2, 11.9% switched from normal to low or high response, and 12.5% switched from low or high to normal response; 75.6% remained in the same category. Between cycles 2 and 3, 15.9% switched from normal to low or high response, and 10.2% switched from low or high to normal response; 73.9% remained in the same category. These shifts are symmetrical in nature, in that the percentage of subjects who shift from normal to low or high response is comparable to the percentage of subjects who shift from low or high to normal response. Baseline FSH and AFC did not significantly predict transition in ovarian response. The variability in ovarian responses between repeated cycles using the same protocol was not explained by baseline FSH and AFC. NCT00696878 Protocol P05714.

The Utility of Menstrual Cycle Length as an Indicator of Cumulative Hormonal Exposure

Associations between menstrual cycle length and chronic diseases are hypothesized to be due to differences in underlying hormonal patterns. The aim of the study was to evaluate the association between menstrual cycle length and the hormonal profile and anovulation. We conducted a prospective cohort study at the University at Buffalo from 2005 to 2007. We recruited 259 healthy, regularly menstruating women aged 18-44 yr. Cycle length was observed for up to two cycles. Serum estradiol, progesterone, LH, and FSH were measured up to eight times per cycle for up to two cycles. Women with short cycles (<26 d) had higher FSH concentrations during menses and in the late luteal phase, higher follicular estradiol concentrations, and lower LH concentrations across the cycle. Among women with longer cycles (>35 d), estradiol and LH peaks occurred on average about 3 d later, and FSH peaks about 1 d later compared to women with normal-length cycles. Both short and long cycles, compared with normal-length cycles, had an increased probability of anovulation. In general, per-cycle exposure to hormones was less in short cycles based on the area under the curve, although over time the cumulative exposure to estradiol would be greater for women with short cycles. Short ovulatory cycles were associated with higher follicular phase estradiol, an earlier rise in FSH, and an increased risk of anovulation. These results suggest that menstrual cycle length may be a relevant indicator of estradiol exposure and risk of anovulation among regularly cycling women.

Absence of seasonal changes in FSHR gene expression in the cat cumulus–oocyte complex in vivo and in vitro

Domestic cat oocytes are seasonally sensitive to FSH. Compared with those collected during the breeding season, oocytes from the nonbreeding (NB) season require more FSH during in vitro maturation to achieve comparable developmental competence. This study tested the hypothesis that this seasonal variation was due to altered expression of FSH receptors (FSHR) and/or FSH-induced genes. Relative expression levels of FSHR mRNA and FSH-enhanced gene estrogen receptor β (ESR2) were measured by qPCR in whole ovaries and immature cumulus-oocyte complexes (COCs) isolated from cat ovaries during the natural breeding vs NB seasons. Expression levels of FSH-induced genes prostaglandin-endoperoxide synthase 2 (PTGS2), early growth response protein-1 (EGR1), and epidermal growth factor receptor (EGFR) were examined in mature COCs from both seasons that were a) recovered in vivo or b) matured in vitro with conventional (1 μg/ml) or high (10 μg/ml) FSH concentrations. Overall, FSHR mRNA levels were lower in whole ovaries during the NB compared with breeding season but were similar in immature COCs, whereas ESR2 levels did not differ in either group between intervals. We observed changes in PTGS2, EGR1, and EGFR mRNA expression patterns across maturation in COCs within but not between the two seasons. The lack of seasonal differentiation in FSH-related genes was not consistent with the decreased developmental capacity of oocytes fertilized during the NB season. These findings reveal that the seasonal decrease in cat oocyte sensitivity to FSH occurs both in vivo and in vitro. Furthermore, this decline is unrelated to changes in expression of FSHR mRNA or mRNA of FSH-induced genes in COCs from antral follicles.

Developmental, but Not Meiotic, Competence of Cat Oocytes Is Affected by Seasonal Anestrus.

Immature cat oocytes collected during seasonal anestrus (August-January) require high FSH concentrations in vitro to achieve nuclear and cytoplasmic maturation. The normally compromised meiotic and developmental competence of these oocytes is not due to reduced FSH-receptor (FSHR) abundance. To better understand the physiological mechanisms of this seasonal difference, we assessed the impact of the seasonal anestrus on oocyte nuclear and cytoplasmic maturation in vivo as well as the expression of maturation-related genes. Twelve adult cats were exposed for 3 to 5 months to a natural breeding season (14 hours of light and 10 hours of dark) and then to a similar interval simulating anestrus (8 hours of light and 16 hours of dark). After ovarian stimulation with exogenous eCG/hCG, oocytes were aspirated from preovulatory follicles by laparoscopy. Grade 1 cumulus-oocyte complexes (COCs; dark oocyte cytoplasm and several layers of expanded cumulus cells) were selected and inseminated (n = 30 during the breeding season; n = 45 during anestrus) with frozen-thawed sperm. Presumptive embryos then were cultured for 8 days, fixed in 70% v/v ethanol and stained with Hoechst to determine the number of blastomeric nuclei. During each interval, a proportion of Grade 1 COCs (n = 8 during the breeding season; n = 11 during anestrus) were collected for relative quantification of maturation-related genes (ESR2, PTGS2, EGFR). Total RNA was extracted using a Picopure RNA isolation kit and cDNA generated using random primers and Superscript III reverse transcriptase. cDNA samples were assessed by real-time qPCR to compare relative expression levels of FSHR, ESR2, PTGS2 and EGFR (normalized to ACTB, RPS7 and YWHAZ expression). Proportions of Grade 1 COCs at the metaphase II stage were similar between the two intervals. Relative expression levels of developmental markers ESR2, PTGS2, EGFR also were comparable. A trend for decreased EGFR expression was associated with a lower proportion of oocytes fertilized and reaching an advanced embryo stage (P<0.05) during anestrus compared to the breeding season. Therefore, although oocyte meiotic competence is unimpaired in vivo, oocyte developmental competence is compromised during the anestrual compared to the breeding season. Generally, this effect on developmental capacity was not reflected in all maturation-related genes. Collective results infer that alternate functions of FSH unrelated to downstream gene regulation (such as EGFR) may be responsible for seasonal decreases in oocyte developmental capacity in vivo. Further investigation of FSHR functionality will identify alternate mechanisms to manipulate FSH responsiveness in vivo. (Supported by the Kelly Fellowship and Lalor Foundation) (poster)

The use of a ‘first-wave’ model to study the effect of nutrition on ovarian follicular dynamics and ovulation rate in the sheep

We have developed an experimental model in which groups of ewes are simultaneously experiencing the first ovarian follicular wave of their oestrous cycle. We used this 'first-wave model' in a 2 × 2 factorial experiment (ten ewes per group) to study the effect of body condition (BC) and a short-term supplement on follicular dynamics and ovulation rate. The 'first-wave' was established by giving ewes three injections of prostaglandin (PG), 7 days apart. The 6-day supplement (lupin grain) began 2 days after the second PG injection and continued until the third. Follicles were studied by ultrasound, and blood was sampled to measure glucose and hormones. The supplement increased (P<0.01) the concentrations of glucose, insulin and leptin, decreased FSH concentrations (P<0.01) and tended to increase oestradiol concentrations (P=0.06). The supplement tended to increase the number of 3 mm follicles (P=0.06). Compared with low-BC ewes, high-BC ewes had more follicular waves (P<0.05), higher concentrations of insulin, leptin and IGF1 (P<0.05) and tended to have higher FSH concentrations (P=0.09). Leptin and insulin concentrations remained high until the end of supplementation in high-BC ewes, whereas they decreased after the third day of supplementation in low-BC ewes. In conclusion, high concentrations of metabolic hormones in fat ewes are associated with the development of more follicular waves. When a supplement is superimposed on this situation, changes in glucose and metabolic hormones allow more follicles to be selected to ovulate.

IVF treatment should not be postponed for patients with high basal FSH concentrations

This study determined the influence of inter-cycle variation of basal FSH concentrations on IVF treatment results, in patients with a history of high basal FSH. Patients underwent at least two IVF cycles, one with basal serum FSH ⩾10IU/l and the other at least 3IU/l lower (interval between cycles being <1year when the second cycle had the elevated FSH). A subanalysis was performed in patients with exceptionally large differences in values (⩾16IU/l and ⩽12IU/l). IVF outcomes were compared according to basal FSH concentrations in two consecutive cycles. Seventy-six patients met the inclusion criteria. Mean basal serum FSH were 15.0±3.6IU/l in the 'high FSH' group (range 12-24IU/l) and 9.0±3.0IU/l in the 'low FSH' group (range 5-14IU/l). Patient age, oestradiol at HCG administration, number of collected oocytes, fertilization and clinical pregnancy rates were similar for all cycles compared. Analysis of the subgroup with exceptionally large differences of basal FSH concentration yielded similar results. Neither high nor low basal serum FSH values were associated with IVF outcome in patients with reduced ovarian reserve and previously determined high basal FSH concentrations. Ovarian stimulation need not be delayed until FSH declines.

Endocrinologic Control of Normal Canine Ovarian Function

In dogs, the termination of the 3-10-month obligate anoestrus involves selection of a cohort of LH-sensitive follicles, presumably from a wave of dominant small antral follicles that would otherwise undergo atresia. The number and size of such follicles appears to increase, especially during the last 50 days of anoestrus when the already elevated concentrations of FSH become further elevated. The final selection and eventual terminal development of these follicles is caused by an increased frequency of high-amplitude LH pulses at the end of anoestrus. Concomitant increases in FSH are typically small or negligible. High concentrations of FSH in anoestrus are likely to be important in maintaining, if not stimulating, overlapping waves of dominant follicles throughout anoestrus, their expression of aromatase activity and basal oestradiol secretion sufficient to suppress LH by negative feedback. An attractive hypothesis is that late anoestrus increases in LH-stimulate synthesis of precursor androgen for already available FSH-dependent aromatase. After 7 or more days of elevated LH, and perhaps 2-5 days of semi-autonomous growth, with maximal oestradiol production reached, follicle capacity to further increase oestradiol becomes limited and excess progesterone becomes increasingly secreted. The pre-ovulatory LH surge and oestrus onset are then triggered - often synchronously and in concert with the terminal maturation of the follicles - by central effects of the large decrease in the oestrogen to progestin ratio. Follicular endocrine and paracrine events during and following the LH surge are likely similar to those reported for other species. The prolonged luteal phase lengths of 55-75 days in non-pregnant bitches bracket the 64 +/- 1 day in pregnancy and represent a genetically programmed luteal cell lifespan approximating gestation length as occurs in the luteal phase of hysterectomized animals of most polyoestrous artiodactyls and rodents. The 30-40-day slow regression after day 20 to 30 involves periodic cell death, diminution in cell size, low levels of apoptosis and minimal or modest involvement of endogenous prostaglandin F (PGF) production. The canine corpus luteum (CL) is dependent on both LH and prolactin as stimulating luteotrophins by day 15, and as required luteotrophins by days 20-25, if not earlier. Thereafter, both luteotrophins likely have cellular mechanisms of action similar to those reported for other species. Progesterone secretion during pregnancy is greatly enhanced by characteristic, and probably relaxin-stimulated, increases in prolactin concentration starting at or after day 25, and persisting to term. Near term, foetoplacental maturation results in the placental release of large, luteolytic amounts of PGF for 1-2 days pre-partum. Pre-partum luteolysis, like that induced by exogenous prostaglandin, likely involves a cascade enhanced by the removal of progesterone inhibition of PGF release and some degree of intra-luteal PGF synthesis. That a likely twofold or greater increase in progesterone production by the CL of pregnancy does not result in significantly higher serum progesterone than in non-pregnant metoestrus relates to several biological changes, including a large increase in plasma volume of distribution, increased metabolism of progesterone by increased uterine, placental and mammary masses and increased liver clearance and excretion of progesterone and progesterone metabolite. Anoestrus length and ovarian cycle intervals, variable within and among bitches, are likely affected by neuroendocrine components of an endogenous circannual cycle, albeit only photo-entrained in the Basenji breed. This may be modified by the prior luteal phase, exposure to oestrus female pheromones and as yet unknown mechanisms that likely operate via inhibitory opioidergic and/or stimulatory dopaminergic hypothalamic pathways affecting late anoestrus increases in LH.

The effect of lead intoxication on endocrine functions

Studies on the effects of lead on the endocrine system are mainly based on occupationally lead-exposed workers and experimental animal models. Although evidence is conflicting, it has been reported that accumulation of lead affects the majority of the endocrine glands. In particular, it appears to have an effect on the hypothalamic-pituitary axis causing blunted TSH, GH, and FSH/LH responses to TRH, GHRH, and GnRH stimulation, respectively. Suppressed GH release has been reported, probably caused by reduced synthesis of GHRH, inhibition of GHRH release or reduced somatotrope responsiveness. Higher levels of PRL in lead intoxication have been reported. In short-term lead-exposed individuals, high LH and FSH levels are usually associated to normal testosterone concentrations, whereas in long-term exposed individuals' low testosterone levels do not induce high LH and FSH concentrations. These findings suggest that lead initially causes some subclinical testicular damage, followed by hypothalamic or pituitary disturbance when longer periods of exposure take place. Similarly, lead accumulates in granulosa cells of the ovary, causing delays in growth and pubertal development and reduced fertility in females. In the parenchyma of adrenals histological and cytological changes are demonstrated, causing changes in plasma basal and stress-mediated corticosterone concentrations and reduced cytosolic and nuclear glucocorticoid receptor binding. Thyroid hormone kinetics are also affected. Central defect of the thyroid axis or an alteration in T4 metabolism or binding to proteins may be involved in derangements in thyroid hormone action. Lead toxicity involves alterations on calcitropic hormones' homeostasis, which increase the risk of skeletal disorders.

Effect of Suppression of FSH with a GnRH Antagonist (Acyline) Before and During Follicle Deviation in the Mare

A GnRH antagonist (Acyline) was used to study the role of FSH in early development of a follicular wave in 61 mares. In Experiment 1, a single dose of 3 mg per mare, compared with 0 and 1 mg, suppressed both the FSH and follicle responses to exogenous GnRH. In Experiment 2, high concentrations of FSH were induced by two successive ablations of all follicles >/= 6 mm on days 10 and 13 (day 0 = ovulation). A single treatment with Acyline resulted in significantly greater suppression of plasma concentrations of FSH than a single treatment with charcoal-extracted follicular fluid (source of inhibin) or oestradiol. Suppression of FSH was not significantly different between the group treated with Acyline alone and a group treated with a combination of Acyline, inhibin and oestradiol. In Experiment 3, all follicles were ablated on day 10 to induce an FSH surge and a new follicular wave. Acyline treatment on day 10 resulted in an immediate decrease in FSH, without a significant effect on day of emergence of a new wave or growth of follicles from 7 to 11 mm on days 11-13. Treatment on day 15, a day before expected follicle deviation and after the peak of the wave-stimulating FSH surge, resulted in an immediate decrease in FSH and cessation of follicle growth. Results indicated that growth of follicles for about 2 days after wave emergence was independent of FSH. In contrast, during the decline in the wave-stimulating FSH surge and before follicle deviation, growth of follicles was dependent on FSH.

Evaluation of Seminal Fluid Parameters, Reproductive Hormones and Testicular Biopsy for non-obstructive Azoospermic Patients with Sertoli cell only Syndrome

The aims of this study were (i) to determine the seminal fluid parameters, levels of serum reproductive hormones, testicular size and diameter of seminiferous tubules depending on multiple testicular biopsies from non-obstructive azoospermic (NOA) patients, and (ii) to assess the effect of smoking on concentrations of serum reproductive hormones. Thirty four NOA patients were involved in the present study. The selection of patients was based on an average of 2 pelleting seminal analysis, reproductive hormones profile and diagnostic testicular biopsy. A detailed questionnaire was used to obtain a thorough history from the patients. The results of this study showed that the mean age of NOA patients with Sertoli cell only syndrome (SCOS) was 33.875 years, and 47.05 % of NOA patients have had 2-4 years duration of infertility. Macroscopic examination of seminal fluid appeared to have normal values as reported by WHO. Non-significant (P&gt;0.05) difference was observed for testicular size and diameter of seminiferous tubules between right and left testis. High and abnormal concentrations of serum FSH were registered for NOA patients with SCOS. However, non-significant (P&gt;0.05) differences were reported for concentrations of serum reproductive hormones between smokers and non smokers. In conclusion, testicular biopsy is the useful and predictable diagnostic tool for NOA patients with SCOS. Further studies are needed to explain the etiology, management and prognosis of NOA patients with SCOS.

Control of estradiol secretion in reproductive ageing

Estradiol (E(2)) concentration is preserved in older reproductive-aged women despite a decrease in follicle number and androstenedione (AD) levels. We hypothesized that increased aromatase activity accounts for E(2) preservation in older women. Older (36-46 years; n = 11) and younger (21-35 years; n = 10) women with 25- to 35-day menstrual cycles participated in a parallel design study. Daily blood samples were drawn starting at menses, and recombinant human FSH (rhFSH), 150 IU, was administered when the dominant follicle's diameter was > or =16 mm. FSH, LH, E(2), estrone (E(1)), AD and the AD/E(1) ratio were compared. E(2) and E(1) concentrations and the E(1)/E(2) ratio were similar across the follicular phase in older compared with younger women, whereas AD and the AD/E(1) ratio were lower. Older women had higher FSH concentrations in the early follicular phase and fewer small follicles. RhFSH-stimulated changes in E(1) were similar between older and younger subjects despite the smaller number of follicles. These findings suggest that E(2) secretion is maintained by increased aromatase function in older compared with younger reproductive-aged women, whereas there is no apparent difference in 17beta-hydroxysteroid dehydrogenase activity. The increased aromatase is probably driven by increased FSH in the early follicular phase and compensates for the decreased follicle number in older reproductive-aged women.

The Relationship of Longitudinal Change in Reproductive Hormones and Vasomotor Symptoms during the Menopausal Transition

The relationship of reproductive hormones to vasomotor symptoms (VMS) has been incompletely explored, although an increase in such symptoms at midlife and their reduction with hormone therapy suggest a strong and direct relationship. Vasomotor symptoms are reported by 65-76% of women traversing the menopausal transition and are a primary reason for medical intervention during this life stage. The purpose of this report was to relate longitudinal serum concentrations of the reproductive hormones estradiol (E2), FSH, testosterone (T), dehydroepiandrosterone sulfate (DHEAS), and SHBG and the free hormone indices free E2 index (FEI) and free T index (FTI) with the occurrence of VMS in women traversing the menopausal transition. The Study of Women's Health Across the Nation is a multisite, longitudinal, cohort study of the menopausal transition being conducted in community-based groups of women. At baseline, 3302 menstruating women who belonged to one of five ethnic/racial groups were recruited and followed up with annual visits. Frequencies of symptoms (hot flashes, night sweats) for the prior 2 wk and measures of other covariates as well as potentially confounding variables were self-reported in the annual interview. Serum was obtained annually, on d 2-5 of a spontaneous cycle in cycling women or within 90 d of the anniversary of the baseline study visit in noncycling women and assayed for FSH, E2, T, SHBG, and DHEAS. FTI and FEI were calculated. This analysis incorporated available longitudinal data from 3293 women, excluding information collected at or after first report of hormone therapy use or hysterectomy. Data were analyzed using longitudinal marginal logistic regression models and a partial proportional odds model. After adjusting for age, body mass index, and other related covariates, VMS prevalence increased with higher (log)FSH concentrations, and the increase was greater when blood was drawn more than 5 d after menses began. FSH concentrations were positively associated with the frequency of either hot flashes or night sweats, and higher FSH concentrations were associated with greater odds of reporting more frequent symptoms. Vasomotor symptom prevalence decreased with higher (log)E2, (sqrt)SHBG, and (log)FEI but only when these hormone values were modeled independently of (log)FSH values and the specimens were obtained outside the d 2-5 window. When modeled simultaneously with (log)FSH, (log)E2, (sqrt)SHBG, and (log)FEI were no longer significantly associated with symptom prevalence. (Cubic root)T and (sqrt)DHEAS concentrations and (log)FTI were not associated with the prevalence of VMS. Annual serum FSH concentrations, but not E2, T, DHEAS, FTI, or FEI when collectively modeled longitudinally, are associated with both the prevalence and frequency of VMS in women at midlife.