Higher LH Concentrations Research Articles

Subacute high-refined carbohydrate diet leads to abnormal reproductive control of the hypothalamic-pituitary axis in female rats

We previously reported that female rats placed on a diet containing refined carbohydrates (HCD) resulted in obesity and reproductive abnormalities, such as high serum LH concentration and abnormal ovarian function. However, the impacts at the hypothalamic-pituitary (HP) function, specifically regarding pathways linked to reproductive axis modulation are unknown. In this study, we assessed whether subacute feeding with HCD results in abnormal reproductive control in the HP axis. Female rats were fed with HCD for 15 days and reproductive HP axis morphophysiology was assessed. HCD reduced hypothalamic mRNA expression (Kiss1, Lepr, and Amhr2) and increased pituitary LHβ+ cells. These changes likely contribute to the increase in serum LH concentration observed in HCD. Blunted estrogen negative feedback was observed in HCD, with increased kisspeptin protein expression in the arcuate nucleus of the hypothalamus (ARH), lower LHβ+ cells and LH concentration in ovariectomized (OVX)+HCD rats. Thus, these data suggest that HCD feeding led to female abnormal reproductive control of HP axis.

SAT-444 Long-Term Effect of Neutering on Plasma Luteinizing Hormone Concentrations in Cats: A Potential Role in the Pathogenesis of Feline Hyperthyroidism

Feline hyperthyroidism remains a major area of interest within the veterinary field given its high prevalence, affecting nearly 10% of geriatric cats, and that causal factors leading to this disease are not completely understood.1,2 Feline hyperthyroidism shares clinical and histopathological similarities with Toxic Multinodular Goitre in humans and therefore the discovery of driving cellular mechanisms behind the pathogenesis of this feline disease may bring translational insight into the pathogenesis of the later.3,4 Gonadotropin hormones such as LH are structurally related to other glycoproteins including TSH and cross-reactivity between these and their receptors has been demonstrated.5 It is hypothesized that increased concentrations of gonadotropins in neutered cats might be implicated in the pathogenesis of hyperthyroidism. This study aimed to determine the long-term effect of neutering on plasma LH concentrations in cats. Stored plasma samples from client-owned cats were used for measurement of LH and TSH concentrations. Clinical data, including age, sex, neutering age and medical history were reviewed. Two study populations were included in this study: (1) a geriatric cat population (≥ 9 years old): 18 entire and 18 neutered cats matched for age, sex and date of sample collection; (2) an adult cat population (2-8 years old): 45 neutered cats. LH concentrations were measured using a feline ELISA and TSH concentrations were measured by the Immulite canine TSH assay. Geriatric neutered cats have higher plasma LH concentrations (median, 0.25 ng/ml [25th percentile, 0.25; 75th percentile, 2.1]) than age matched entire cats (0.25 ng/ml [0.25, 0.25], P < 0 .001). Cats neutered between 6-9 months of age have higher LH concentrations than cats neutered before or after that period (P = 0.004). No correlation was found between plasma LH and TSH concentrations (P = 0.422). In conclusion, neutering causes significant long-term increase in LH concentrations in cats. Further research to determine whether this results in activation of the TSH receptor and ultimately in thyrocyte hyperplasia and/or hyperfunction is warranted.

373 Response to kisspetin as a possible reference for puberty age in heifer

Abstract The objective of this study was to compare the variation of LH concentrations in response to kisspeptin as a way to evaluate the neuroendocrine maturation of Nellore heifers. The hypothesis was that the LH response to kisspeptin increases with age as the number of kisspeptin receptors increase in the CNS. Initially 50 weaned heifers were segregated according to the weaning weight as light (174±1 kg) or heavy (232±2 kg). Both groups received a kisspeptin injection (10μg/kg; IM) monthly from weaning to 16 months, and blood samples were collected 20 minutes after each application. After 16 months of age, heifers were exposed to bulls (25:1) for 60 days and pregnancy was determined 30 days after the end of the breeding season. The LH concentration in response to kisspeptin increased over time (P = 0.001), but there was no difference between light and heavy heifers over the 8-month period (3.62±0.14, 3.34±0.16 ng/ml; P = 0.3853). Similarly, no differences were observed between heifers that became pregnant or not (3.42±0.12, 3.67±0.20 ng/ml; P = 0.3169). Due to the high LH concentrations at 8 months of age (3.06±0.19 ng/ml), another experiment was performed in younger heifers. Fifty newborn Nellore heifers (29±0.3 kg) from the same herd received monthly injections of kisspeptin until weaning. There was also an increase in LH concentrations in response to kisspeptin over time (P = 0.001), but the mean LH concentrations in this experiment (4.05±0.22ng/mL) were considerably greater than those in postweaning heifers. Our interpretation is that genetic differences likely contributed to the different responses to kisspeptin between the two experiments. In order to test this hypothesis, the LH response to kisspeptin will be evaluated in a large number of animals from different herds at weaning to determine the effect of genetic variability on kisspeptin response and possibly to use this phenotype as a marker for age at puberty.

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.

448 The effects of a novel follicle wave and heat synchronization protocol on the follicles, circulating hormones, and estrus of Aanestrous ewes

Reproductive performance in seasonally anestrous ewes is poor even after the use of current controlled breeding protocols. Anestrous ewes treated with a medroxyprogesterone acetate sponge, for 12 or 14 d, and estradiol-17β (E2) have synchronized follicular wave emergence. The objective of this study was to determine the effects of an E2 injection 6 d after CIDR insertion on follicles, E2 and LH concentrations, and estrus in seasonally anestrous ewes. Ewes (n = 13) received CIDRs (Day -12) followed by an injection of eCG (500 IU; i.m.; Day 0) at CIDR removal and an injection of sesame oil without (1 mL; i.m.; Control) or with E2 (350µg; i.m.; Day -6) 6 d before CIDR removal. Treatments were balanced for age, parity, and BCS. Blood samples were collected every 6 h for 48 h after E2 injection and every 3 h for 60 h starting 18 h after eCG injection to determine LH concentrations. Blood samples were collected on Day -6 and 0 and every 6 h for 60 h starting 18 h after eCG injection to determine E2 concentrations. Ovarian ultrasonography was done on Day -6 and 0. A ram was introduced on Day 1 to observe estrus. Ewes treated with E2 had higher LH concentrations (0.37 ± 0.05 ng/mL) than ewes treated with oil alone (0.12±0.05 ng/mL) during the 48 h after E2 injection (P < 0.005). Concentrations of LH were highest at 18 h after E2 injection (1.11 ± 0.12 ng/mL; P < 0.001). Ewes treated with E2 had higher LH concentrations (2.10 ± 0.18 ng/mL) than ewes treated with oil alone (0.12 ± 0.16 ng/mL) at 18 h after E2 injection (P < 0.001). The interval from eCG injection to the start of the pre-ovulatory LH surge was similar (37.1 ± 4.4 h; P > 0.05), but was more synchronized in ewes treated with E2 (2.3 ± 0.6 h) than ewes treated with oil alone (12.0 ± 5.1 h; P < 0.01). Concentrations of E2 were similar between treatments on Day -6 (2.1 ± 0.3 pg/mL; P > 0.05) and Day 0 (2.3 ± 0.4 pg/mL; P > 0.05). Concentrations of E2 tended to be highest at 18 h after eCG injection (3.5 ± 0.5 pg/mL; P = 0.076). Maximum follicular diameter was larger on Day 0 (4.8 ± 0.2 mm) than Day -6 (3.4 ± 0.2 mm; P < 0.001). There were no differences in the interval from eCG treatment to the start (37.6 ± 2.7 h) or end (74.7 ± 1.9 h) of estrus (P > 0.05). Adding an E2 treatment during a CIDR-eCG estrus synchronization protocol increased LH concentrations after E2 treatment and stimulated a more synchronized pre-ovulatory LH surge in seasonally anestrous ewes.

Characterization of the variability and repeatability of gonadotropin-releasing hormone-induced luteinizing hormone responses in dairy cows within a synchronized ovulation protocol.

The primary objective was to determine the variability and repeatability of GnRH-induced LH responses. The secondary objective was to evaluate the associations among plasma LH, FSH, estradiol (E2), and progesterone (P4) concentrations. One hundred lactating Holstein cows (35 primiparous, 65 multiparous) were initially subjected to a presynchronization protocol (d 0, PGF2α; d 3, GnRH) followed 7 d later by Ovsynch (d 10, GnRH; d 17, PGF2α; 56 h later, GnRH) and timed artificial insemination 16 h after the last GnRH. Blood samples were collected immediately before the GnRH injection of presynchronization and the second GnRH of Ovsynch to determine plasma concentrations of LH, FSH, and P4. A second blood sample was collected 2 h after each of the above GnRH injections to determine GnRH-induced LH and FSH concentrations. Plasma concentrations of E2 were also determined in samples collected immediately before the second GnRH of Ovsynch. Cows that (1) had higher LH concentrations at 0 h than at 2 h after GnRH, (2) showed an ongoing spontaneous LH surge, (3) did not respond to GnRH, and (4) had P4 ≥ 0.5 ng/mL at GnRH of presynchronization and the second GnRH of Ovsynch were excluded from the analysis. The variability (coefficient of variation) and repeatability [between animal variance/(within animal variance + between animal variance)] of GnRH-induced LH response were determined from samples collected 2 h after the GnRH of presynchronization and the second GnRH of Ovsynch. The associations among plasma LH, FSH, E2, and P4 were determined at the second GnRH of Ovsynch. Mean (±SEM) LH concentrations before GnRH were 0.5 ± 0.04 and 0.6 ± 0.03 ng/mL, whereas mean LH concentrations 2 h after GnRH were 9.8 ± 1.0 and 12.1 ± 0.8 ng/mL at GnRH of presynchronization and the second GnRH of Ovsynch, respectively. The variability of GnRH-induced LH was 76.1 and 52.1% at GnRH of presynchronization and the second GnRH of Ovsynch, respectively. The repeatability estimate for GnRH-induced LH concentration between GnRH of presynchronization and Ovsynch assessments was 0.10. Plasma concentrations of LH were positively associated with FSH and E2 (r = 0.61 and 0.30, respectively) and negatively associated with P4 (r = -0.46) at the second GnRH of Ovsynch. In summary, GnRH-induced LH responses were highly variable and unrepeatable, and LH concentrations were positively associated with FSH and E2 and negatively associated with P4.

Inhibitory effects of mitotane on viability and secretory activity in mouse gonadotroph cell lines

Mitotane represents the mainstay medical treatment for metastatic, inoperable or recurrent adrenocortical carcinoma. Besides the well-known adverse events, mitotane therapy is associated also with endocrinological effects, including sexual and reproductive dysfunction. The majority of male patients undergoing adjuvant mitotane therapy show a picture of hypogonadism, characterized by low free testosterone and high sex hormone binding globulin levels and unmodified LH concentrations. Since mitotane has been shown to have direct pituitary effects, we investigated whether mitotane may influence both cell viability and function of gonadotroph cells in the settings of two pituitary cell lines. We found that mitotane reduces cell viability, induces apoptosis, modifies cell cycle phase distribution and secretion of gonadotroph cells. The present data strengthen previous evidence showing a direct mitotane effect at pituitary level and represent a possible explanation of the lack of LH increase following decrease in free testosterone in patients undergoing adjuvant mitotane therapy.

The pattern of cervical penetration and the effect of topical treatment with prostaglandin and/or FSH and oxytocin on the depth of cervical penetration in the ewe during the peri-ovulatory period

Artificial insemination in sheep has two major limiting factors: the poor quality of frozen-thawed ram semen and the convoluted anatomy of the sheep cervix that does not allow transcervical passage of an inseminating catheter. It has been demonstrated that in the ewe during estrus, there is a degree of cervical relaxation mediated by ovarian and possibly gonadotrohic hormones, and we set out to investigate factors that might enhance cervical relaxation. Five experiments were conducted on ewes of different breeds to determine: 1) the pattern of cervical penetration during the periovulatory period in ewes of several breeds (Welsh Mountain, Île-de-France, Vendéenne, Romanov and Sarda); 2) the effect of the “ram effect” a socio-sexual stimulus, on cervical penetration; and 3) the effects of the intracervical administration of follicle-stimulating hormone (FSH), oxytocin and a prostaglandin E agonist (misoprostol) on the depth of cervical penetration during the periovulatory period. The results showed that during the periovulatory period in all breeds examined, there was increased penetration of the cervical canal (P < 0.05) by an inseminating catheter. Cervical penetration increased to a maximum 54 h after the removal of progestagen sponges and then gradually declined. Furthermore, the depth of cervical penetration but not its pattern, was affected (P < 0.05) by the breed of ewe. The maximum depth of cervical penetration was lower (P < 0.05) in the Vendéenne breed compared to the Île-de-France and Romanov breeds, which did not differ from one another. In the presence of rams, the depth of cervical penetration was increased at 48 and 54 h after removal of sponges (P < 0.05) and reduced at 72 h (P < 0.05). The local administration of hormones FSH, misoprostol (a PGE agonist) and oxytocin alone and in various combinations did not have any significant effect on the depth of cervical penetration during the periovulatory period. In conclusion, the natural relaxation of the cervix observed in ewes of several breeds occurs at a time during estrus, 54 h after the removal of progestagen sponges, which is the most suitable for artificial insemination. The effect was enhanced by the presence of a ram but not by the local intracervical administration of FSH, misoprostol and oxytocin even though oxytocin and PGE2 are involved in cervical function. The time of maximum cervical penetration in the preovulatory period (54 h) coincides with high LH and estradiol concentrations suggesting they might be responsible for the relaxation of the cervix probably through an oxytocin-PGE mediated pathway.

Ovulating induction methods in rabbit does: The pituitary and ovarian responses

The aim of this study was to compare the pituitary and ovarian responses in rabbit does subjected to different methods of ovulation induction. Forty-eight receptive females were randomly distributed into six groups (N = 8) and were inseminated with standard glass catheters. Buserelin intramuscular (BM) does were inseminated using a pool of fresh heterospermic semen and an intramuscular injection of 1 μg of buserelin acetate to induce ovulation. Buserelin intravaginal (BV) does were inseminated in a similar way, but ovulation was induced with the GnRH analogue (10 μg of buserelin acetate) combined with 0.5 mL of semen extender. The raw semen (R) and saline groups (S) were inseminated with undiluted semen or saline, respectively, without any inducer of ovulation. Another group (A) received lumbar anaesthesia (1.5 mL of 2% lidocaine), and only the empty catheter was introduced into the vagina. The AR does were treated the same way as group A but were inseminated with raw semen instead of an empty catheter. Blood samples were collected to determine the LH concentrations before and after AI (30, 60, 90, and 120 minutes). Ovulation, pregnancy, and conception rates were determined after euthanasia on day 14 post AI. Ovulating does had higher mean LH concentrations than nonovulating does (197.9 vs. 45.9 ng/mL; P < 0.05). The ovulation rates of buserelin intramuscular and intravaginal does were 100%, and the pregnancy rates were 87.5% and 100%, respectively. Rabbit does in groups A and AR did not ovulate and had similar mean plasma LH concentrations after 60 minutes compared with the S group (49.4 and 49.2 ng/mL vs. 41.6 ng/mL, respectively), which reached ovulation and pregnancy rates of 37.5%. Does inseminated only with raw semen had an ovulation rate of 75% and a pregnancy rate of 62.5%; they also demonstrated higher plasma LH concentrations than does of the S, A, and AR groups. In conclusion, ovulation in rabbit does can be induced by exogenous GnRH administration (im and intravaginal). The high plasma LH concentration and ovulation rate in the R group with respect to the S and A groups could weakly indicate the presence of some molecules in the seminal plasma that could act on or be absorbed by vaginal mucosa. Sensory stimulation and “seminal factors” probably exert a synergy on the ovulation response as demonstrated by the comparison of LH release and the ovulation response in the R, S, RA, and A groups.

No association between endogenous LH and pregnancy in a GnRH antagonist protocol: part II, recombinant FSH

The association between endogenous LH concentrations during ovarian stimulation in a gonadotrophin-releasing hormone (GnRH) antagonist protocol and pregnancy likelihood was examined in a large combined analysis of individualized patient data obtained after treatment with recombinant FSH and a GnRH antagonist prior to IVF/intracytoplasmic sperm injection. Data from 1764 patients from six randomized controlled trials were pooled for retrospective analysis. Ongoing pregnancy and miscarriage rates for patients stratified by LH percentiles were assessed. Patients in the lowest LH quartile (<P25) were younger with a higher predicted ovarian reserve and response compared with patients in the highest quartile (>P75). With adjustment for identified predictive factors of pregnancy, estimated odds ratios (95% confidence interval) for ongoing pregnancy for LH categories <P25 versus ⩾P25, >P75 versus ⩽P75 and <P25 versus >P75 were 0.96 (0.75–1.22), 1.13 (0.88–1.45) and 0.89 (0.66–1.21) on stimulation day 8, and 0.96 (0.76–1.21), 1.03 (0.82–1.30) and 0.95 (0.72–1.26) on the day of human chorionic gonadotrophin, respectively. No significant differences in pregnancy or miscarriage rates between the LH categories were observed. Endogenous LH concentrations have no association with the likelihood of ongoing pregnancy in women undergoing ovarian stimulation using a recombinant FSH/GnRH antagonist protocol. Circulating concentrations of LH are suppressed during ovarian stimulation for IVF/intracytoplasmic sperm injection with either gonadotrophin-releasing hormone (GnRH) agonists or antagonists to prevent premature LH rises. The association between circulating LH concentrations during ovarian stimulation and the likelihood of pregnancy was examined in a large combined analysis of individualized patient data obtained after treatment with recombinant FSH to stimulate multifollicular development and a GnRH antagonist (ganirelix) to prevent LH surges. Data from 1764 patients from six randomized controlled trials were pooled for retrospective analysis. Patients were divided into three groups based on their circulating LH concentrations being either low, normal or high on stimulation day 8 and on the day of human chorionic gonadotrophin (HCG) administration, and their ongoing pregnancy and miscarriage rates were calculated. Patients with low LH concentrations were in general younger, had a higher ovarian reserve and more retrieved eggs than patients with high LH concentrations. With adjustment for factors known to affect pregnancy, the chance of ongoing pregnancy was not lower for patients with low or high LH concentrations on stimulation day 8 or day of HCG administration. No significant differences in miscarriage rates between the LH categories were observed either. This combined analysis confirms that the concentrations of circulating LH during GnRH antagonist treatment do not affect the likelihood of ongoing pregnancy in women undergoing ovarian stimulation with recombinant FSH.

Follicle and systemic hormone interrelationships during induction of luteinized unruptured follicles with a prostaglandin inhibitor in mares

The objective was to determine differences in follicle and reproductive hormone characteristics in mares with ovulatory and flunixin meglumine (FM)-induced anovulatory cycles. Estrous mares were given 1500 IU hCG when the follicle was ≥ 32 mm (0 h). In Experiment 1, control mares (n = 7) were not treated further. The remaining mares (n = 11) were given 1.7 mg/kg FM i.v. twice daily, from 0 to 36 h after hCG treatment. Blood samples and ultrasonographic examinations were performed every 12 h. All control mares ovulated normally between 36 and 48 h. In contrast, eight of 11 FM mares did not ovulate, but developed luteinized unruptured follicles (LUFs). Three FM-treated mares did not develop conventional LUFs. Plasma progesterone concentrations were lower (P < 0.05) in LUF mares at 96, 120, and 216 h than in controls, whereas plasma LH concentrations were higher (P < 0.05) between 108 and 120 h in LUF mares than in controls. Plasma concentrations of PGFM and estradiol did not differ significantly between groups. In Experiment 2, the three mares that did not develop LUFs were treated, during the consecutive cycle, with the same dose of FM but with increased frequency at zero, 12, 24, 30, 36, and 48 h after hCG. One mare formed a LUF, whereas the other two did not. These two mares had lower LH concentrations than LUF or control mares in the two consecutive cycles. In conclusion, systemic treatment with FM blocked ovulation in 73% of treated mares. Mares with LUFs had lower progesterone and higher LH concentrations than control mares.

Comparison of testosterone and insulin-like peptide 3 secretions in response to human chorionic gonadotropin in cultured interstitial cells from scrotal and retained testes in dogs

Levels of testosterone and insulin-like peptide 3 (INSL3) secretions in response to different doses of human chorionic gonadotropin (hCG) in cultured interstitial cells were compared between retained and scrotal testes in dogs. Retained ( n = 10) and scrotal ( n = 9) testes were obtained from small-breed dogs. The testicular tissues were dispersed in Dulbecco's Modified Eagle Medium with Ham's nutrient mixture containing 2000 PU/ml dispase II and 10% fetal bovine serum. The cells were plated with differing concentrations (0–10 IU/ml) of hCG for 18 h in multiwell-plates. Testosterone and INSL3 in the same spent medium were measured by enzyme-immunoassays (EIA). A new EIA with a reliable detection range of 0.025–5 ng/ml was developed in order to measure canine INSL3 in culture medium. Dose-dependent stimulation of testosterone by hCG was observed in the cells of both retained and scrotal testes. The incremental rate of testosterone secretion was significantly lower at 0.1, 1 and 10 IU/ml hCG in the cells of retained testes than in scrotal testes, however. INSL3 secretion was significantly stimulated at 10 IU/ml hCG relative to unstimulated controls comprising cells of scrotal testes; no such stimulation was observed in the cells of retained testes. At 10 IU/ml hCG, the incremental rate of INSL3 was significantly lower in the cells of retained testes than scrotal testes. These results suggest that LH-induced secretory testosterone and INSL3 responses are lower in the interstitial cells of retained testes than of scrotal testes. Furthermore, the high concentrations of LH may acutely stimulate INSL3 release in scrotal testes of dogs, but not in retained testes.

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.

Use of Metformin in Clomiphene Citrate (CC) Resistant Polycystic Ovary Syndrome (PCOS)

Abstract Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting between 4% and 8% of reproductive aged women. Although the symptoms and signs of PCOS are very heterogeneous, the syndrome usually presents with any combination of the following, menstrual irregularities (usually oligomenorrhea or amenorrhea), signs of hyperandrogenism (hirsutism, acne, alopecia) a characteristic appearance of the ovaries on ultrasound examination and an endocrine disturbance often involving high serum concentrations of LH and androgens. There is a well established association between PCOS, insulin resistance and hyperinsulinemia. Insulin resistance is a pivotal defect in PCOS probably counts as one of the most important advances in the battle to control the disorder. This metabolic abnormality leads to a compensatory increase in circulating insulin and this elevated insulin level directly stimulates the ovary to produce excess androgens. It also decreases hepatic sex hormone binding globulin (SHBG), so increasing biologically available free testosterone concentration in the circulation. This metabolic derangement leads to oligomenorrhea and anovulation. Different insulin sensitizers are used to revert the hyperinsulinemic condition. Metformin is top of them, which proved to enhance ovulation in insulin resistant PCOS when used with different ovulation inducing agents. Metformin reduces insulin resistance of peripheral tissue and allows muscle and adipose cells to take in glucose at normal insulin levels. It inhibits hepatic glucose production, decreases intestinal absorption and promotes glucose uptake, utilization by peripheral tissues at the postreceptor level. In this way it reduces insulin level and subsequently androgen level. It is easily available, safe and no teratogenic or adverse fetal outcome were reported by any researcher. It can be used safely in clomiphene resistant PCOS patients.

Role of the endocrine profile for the achievement of pregnancy with IVF

The predictive value of pre-ovulatory hormones for achievement of pregnancy has been extensively evaluated in assisted reproductive technologies. Currently, no high-quality evidence exists to support or deny an association between oestradiol levels on the day of human chorionic gonadotrophin (HCG) administration and pregnancy achievement in IVF cycles. Retrospective studies appear to support the lack of such an association. Progesterone elevation on the day of HCG administration does not appear to be associated with the probability of clinical pregnancy in women undergoing IVF. Finally, no retrospective studies exist to suggest that low endogenous midfollicular LH concentrations are associated with a significantly decreased probability of ongoing pregnancy beyond 12 weeks of gestation in IVF. In two prospective studies, high endogenous LH concentrations during down-regulation were associated with a decreased probability of ongoing pregnancy beyond 12 weeks of gestation. Existing studies evaluating the association between single measurements of pre-ovulatory hormones and the achievement of pregnancy are of low quality and cannot lead to solid conclusions. Based on the available literature, it appears that no association exists between single assessments of oestradiol, progesterone or LH, and pregnancy achievement.

Influence of different concentrations of LH and FSH on in vitro caprine primordial ovarian follicle development

The roles of gonadotrophins in the regulation of primordial ovarian follicular development remains unclear. The aims of the present study were to investigate the effects of LH alone or in combination with FSH on the survival, activation and growth of in vitro caprine primordial follicles, using histology and transmission electron microscopy (TEM). To this end, samples of the caprine ovarian cortex were cultured for 1 or 7 days (39 °C), in an atmosphere of 5% CO 2, in minimum essential medium (MEM—control medium) supplemented with different concentrations of LH (0, 1, 5, 10, 50 or 100 ng/ml—Experiment 1). In Experiment 2, the control medium was supplemented with FSH (50 ng/ml) and the different concentrations of LH (0, 1, 5, 10 or 50 ng/ml also used). Small samples of non-cultured ovarian tissue, as well as those cultured for 1 or 7 days in a specific medium were processed for classical histological evaluation and TEM to evaluate the follicular integrity and to calculate the percentage of normal follicles. Additionally, the effects of FSH on the oocyte and follicle diameters of the cultured follicles were evaluated. Results showed that after 7 days of culture, the presence of LH (10, 50 or 100 ng/ml) in the culture media significantly increases the percentage of developing follicles ( P < 0.05). In addition, fragments cultured in media supplemented with FSH alone or FSH plus LH had a higher percentage of developing follicles after 1 and 7 days of culture, compared to the control ( P < 0.05). At the end of culture period, 1 and 5 ng/ml LH increased the follicular diameter, while the addition of 1, 5 or 10 ng/ml LH increased the oocyte diameter ( P < 0.05). A combination of FSH with 1 and 5 ng/ml LH increased the follicular diameter. With regard to follicle survival, low doses of LH (1 ng/ml) maintained follicle viability—similar to day 0 and in the control medium after 7 days of culture. However, higher concentrations of LH (5, 10, 50 and 100 ng/ml) induced atresia in the goat follicles. Culture of the ovarian cortex for 7 days in medium supplemented with FSH alone or FSH plus 1 ng/ml LH kept the ultrastructural characteristics of follicles similar to that of day 0. In conclusion, it can be said that, the addition of low concentrations of LH (1 ng/ml) combined with or without FSH maintained the goat follicular ultrastructural integrity, but LH in doses higher than 5 ng/ml induced atresia in in vitro goat preantral follicles.

Concentrations de l’hormone lutéinisante et de la progestérone chez des vaches zébus Azawak soumises à différents protocoles de synchronisation de l’oestrus

Quinze vaches zébus Azawak ont été soumises à deux protocoles de synchronisation de l’oestrus. Les concentrations plasmatiques de LH et le pourcentage des femelles ayant exhibé un comportement d’oestrus ont été répertoriés. Le premier traitement de synchronisation (T1, n = 9) a été effectué avec des implants sous-cutanés de norgestomet placés sous la peau de l’oreille pendant 10 jours. Le traitement a été complété par des injections de valérate d’oestradiol, de prostaglandine F2α et de pregnant mare serum gonadotropin (PMSG). Le deuxième protocole (T2, n = 6) a consisté en deux injections de prostaglandine F2α à 11 jours d’intervalle, suivies d’une injection de PMSG deux jours après la deuxième injection de prostaglandine. Des échantillons de sang ont été prélevés à trois heures d’intervalle pendant cinq jours après le retrait de l’implant (T1) ou l’injection de PMSG (T2) pour mesurer les taux de LH. Le taux d’oestrus induit a été plus élevé chez les vaches du groupe T2, mais cette différence n’a pas été significative. En général, le temps observé entre la fin du traitement et le début de l’oestrus a été plus court chez les femelles traitées au norgestomet (35,9 ± 3,9 h) que chez celles traitées à la prostaglandine (49,5 ± 5,8 h). Sept sur les neuf femelles traitées au norgestomet et seulement deux sur les six traitées à la prostaglandine ont présenté un pic de LH. L’intervalle moyen entre la fin des traitements et le pic de LH a eu tendance à être plus long chez les femelles traitées à la prostaglandine que chez celles traitées au norgestomet. Une femelle a présenté des concentrations de LH anormalement élevées après le retrait de l’implant. Toutefois, aucun pic de LH n’a été observé pendant la période de suivi.

Induction of haemorrhagic anovulatory follicles in mares

A follicular wave and luteolysis were induced in mares by ablation of follicles > or =6 mm and treatment with prostaglandin F(2alpha) (PGF) on Day 10 (where ovulation = Day 0). The incidence of haemorrhagic anovulatory follicles (HAFs) in the induced waves (20%) was greater (P < 0.007) than in preceding spontaneous waves (2%). Hormone and follicle dynamics were compared between induced follicular waves that ended in ovulations (ovulating group; n = 36) v. HAFs (HAF group; n = 9). The day of the first ovulation or the beginning of HAF formation at the end of an induced wave was designated as post-treatment Day 0. The mean 13-day interval from Day 10 (PGF and ablation) to the post-treatment ovulation was normalised into Days 10 to 16, followed by Day -6 to Day 0 relative to the post-treatment ovulation. Concentrations of LH were greater (P < 0.05) in the HAF group than in the ovulating group on Days 10, 11, 12, 14, -3 and -2. The HAF group had greater (P < 0.003) LH concentrations on Day 10 of the preceding oestrous cycle with spontaneous ovulatory waves. The diameter of the largest follicle was less (P < 0.05) in the HAF group on most days between Day 13 and Day -1 and this was attributable to later (P < 0.002) emergence of the future largest follicle at 6 mm in the HAF group (Day 12.4 +/- 0.5) than in the ovulating group (Day 11.3 +/- 0.1). The results indicate that the high incidence of HAFs after PGF and ablation was associated with later follicle emergence and immediate and continuing greater LH concentration after PGF treatment, apparently augmented by an inherently high pretreatment LH concentration.

Seasonal changes in semen characteristics, hormonal profiles and testicular activity in Zaraibi goats

Ten Zaraibi buck goats were used to study the effect of season on semen quality. Bucks were housed and fed according to standard recognized practices. Semen was collected twice a week for 7 consecutive weeks (starting from the 3rd to the 9th week) in the mid of the each season. During these periods scrotal circumference was measured fortnightly. The number of mounts terminating in ejaculation and the time interval between the first mount and ejaculation were also recorded. The physical parameters of semen and semen index (semen volume × spermatozoa concentration/ml × live spermatozoa% × progressive motility%) were measured for the first and the second ejaculates of each semen collection during the week. At the end of each season, testicular biopsies were obtained surgically from three bucks for histological evaluation. Plasma testosterone, FSH and LH concentrations were also determined twice weekly. Bucks demonstrated the highest libido in summer, using the least ( P < 0.01) number of mounts and a shorter ( P < 0.01) reaction time. This coincided with a higher ( P < 0.01) level of plasma testosterone (10 ng/ml) and the best semen quality (semen index: 3354 × 10 6). During autumn, bucks recorded the highest ( P < 0.01) ejaculate volume (0.98 ml) and the maximum output of sperm (4565 × 10 6), as well as a lower ( P < 0.01) percentage of sperm abnormalities (8.8%). This was accompanied by high concentrations of plasma LH (average 2.9 mIU/ml). The histological structure of the testis indicated that during autumn (natural breeding season) seminiferous tubules (Sta) occupied the majority of the testicular tissues (76.6%) and the spermatic layers were highest. It can be said that Zaraibi bucks have distinct seasonal activity, with poor semen characteristics during winter and spring—which may be a critical obstacle for implementing intensive systems of three kidding in 2 years when natural mating is applied.

Clomiphene citrate—end of an era? a mini-review

The purpose of this review is to examine whether the time has come to replace clomiphene citrate (CC) as the first line therapy for WHO group II (eu-oestrogenic) infertility, the majority of which is associated with polycystic ovary syndrome. CC has been the first line therapy for these cases for the last 40 years. It is a simple, cheap treatment, almost devoid of side effects which yields a single live birth rate of approximately 25% of starters. Non-response to CC and the gap between ovulation and pregnancy rates have variously been attributed to its anti-estrogen effects, and high LH and androgen concentrations. Three possible contenders for the replacement of CC as first-line treatment are scrutinized: metformin, aromatase inhibitors and low-dose FSH. Each has their advantages and disadvantages, but none of them, while showing much potential promise, has been proven, as yet, to be a feasible replacement for CC in this role. For CC, it may not yet be the end of an era but it may be the beginning of the end.