Significant Increase In Luteinizing Hormone Research Articles

The LH endocrine profile in gonadotropin-releasing hormone analogue cycles

Research question: What does the evolution of serum luteinizing hormone (LH) levels look like throughout the follicular phase of cycles in which gonadotrophins and gonadotropin-releasing hormone (GnRH) analogues in the context of ovarian stimulation for assisted reproduction technologies (ART) were used? Design: This was a retrospective, observational cohort study in a tertiary infertility clinic. 1303 patients aged between 18 and 43 years of age were included with a total of 2200 cycles for ART, using GnRH-analogues for pituitary down-regulation stimulated with human menopausal gonadotropin (hMG) or recombinant follicle stimulating hormone (rec-FSH). Follicular evolution of LH during ovarian stimulation in different treatment protocols was modeled as repeated measures. Results: LH evolution showed a significant decrease in antagonist/hMG cycles of 0.17 IU/L per day (95% CI [-0.20, −0.12]) and 0.26 IU/L per day in rec-FSH cycles (95% CI [-0.29, −0.22]). This decrease was significantly stronger in rec-FSH cycles than in hMG cycles (estimated difference of 0.09 IU/L per day, 95% CI [0.04, 0.15]). Short agonist/hMG cycles showed a significant increase in LH of 0.04 IU/L per day (95% CI [0.01, 0.08]), while the increase of 0.01 IU/L per day in cycles with rec-FSH was not significant (95% CI [-0.08, 0.10]). Conclusion: Follicular evolution of LH during controlled ovarian stimulation differs between different GnRH analogue cycles. A statistically significant decrease in LH was shown in GnRH antagonist cycles being more pronounced with rec-FSH compared to hMG. This decrease in LH in antagonist cycles and the potential impact on estradiol levels and follicle growth needs further examination.

P-668 The LH endocrine profile in Gonadotropin-Releasing Hormone analogue cycles

Abstract Study question What does the evolution of luteinizing hormone (LH) throughout the follicular phase look like in different treatment protocols for ovarian stimulation in IVF/ICSI? Summary answer Evolution of LH during the follicular phase of ovarian stimulation differs between Gonadotropin-Releasing Hormone (GnRH) analogues, with a significant decrease of LH in antagonist cycles. What is known already Physicians aim to tailor ovarian stimulation protocols to the patient, with protocols varying in type of GnRH analogue and gonadotropin. However, there is no clear consensus on the best treatment protocol and especially the role of LH is still not completely understood as earlier studies focused mainly on suppressing LH levels. Literature has since indicated that excessively suppressed LH levels could be detrimental for clinical outcomes. Research on LH is hampered by multiple measurements during the cycle, different treatment schedules and patients switching schedules over time. Study design, size, duration This was a non-interventional, retrospective, observational cohort study. 2200 ovarian stimulation cycles for assisted reproduction were analyzed, in 1303 individual patients. Patients were treated during the period of January 1st 2015 until September 30th 2020. Cycles were included if the patient was between 18 and 43 years of age, stimulated with human menopausal gonadotropin (hMG) or recombinant follicle stimulating hormone (rec-FSH, follitropin α or β) and using GnRH analogues. Participants/materials, setting, methods Data were extracted from two databases used at a tertiary infertility clinic. Cycles were divided into six treatment protocols: GnRH antagonist/hMG (13.8%), antagonist/rec-FSH (19.7%), long agonist/hMG (35.7%), long agonist/rec-FSH (4.8%), short agonist/hMG (22.5%) and short agonist/rec-FSH (3.5%). 59.5% of cycles were pretreated with an oral contraceptive pill (OCP). LH evolution was visualized by plotting LH levels against the days of the follicular phase and repeated daily LH measures were fitted with a linear mixed model. Main results and the role of chance Basal LH was significantly lower in antagonist/hMG cycles pretreated with OCP compared to no pretreatment (estimated difference -1.23 IU/L, p < 0.001). Mean LH value throughout the follicular phase was significantly lower with OCP pretreatment in antagonist/hMG (estimated difference -1.05 IU/L, p < 0.001) and antagonist/rec-FSH cycles (estimated difference -0.52 IU/L, p < 0.001). When LH evolution throughout the follicular phase was analyzed, no significantly different evolution between cycles with and without OCP was detected (all p > 0.1). Hence further analysis of the LH profiles was performed in the six protocol groups making no distinction between OCP use or not. LH evolution was significantly different between all six protocol groups (p < 0.001). In antagonist/hMG cycles, LH values showed a significant decrease of 0.17 IU/L per day (p < 0.001). In antagonist/rec-FSH cycles, the decrease per day was 0.26 IU/L (p < 0.001).The decrease in LH was significantly larger in rec-FSH cycles than hMG (estimated difference 0.09 IU/L per day, p < 0.001). Short agonist/hMG cycles showed a significant increase in LH of 0.04 IU/L per day (p = 0.002), while the increase of 0.01 IU/L per day in rec-FSH cycles was not significant (p = 1.00). In long agonist cycles, no significant in- or decrease in LH values during the follicular phase was found (p = 1.00). Limitations, reasons for caution Stimulation protocols were chosen by the treating physician which is a limitation of the retrospective design. The authors were able to partly respond to this limitation by adjusting for age and using different cycles per patient in all mixed models. Wider implications of the findings Using profiles to show LH evolution allowed the visualization of the decrease in the evolution of LH in antagonist cycles, even more pronounced in cycles stimulated with rec-FSH compared to hMG. This decrease in LH and the potential impact on estradiol levels and follicle growth needs further examination. Trial registration number not applicable

Effect of Metformin on Anthropometric Measurements and Hormonal and Biochemical Profile in Patients with Prediabetes.

Objectives Metformin is the most widely preferred first-line oral antidiabetic agent that results in clear benefits in blood sugar regulation and diabetes-related complications. This study is aimed at assessing the effect of metformin on anthropometric, hormonal, and biochemical parameters in patients with prediabetes or insulin resistance. Methods A prepoststudy was conducted among 52 patients with prediabetes or insulin resistance who met the inclusion criteria. Weight, body mass index (BMI), and waist circumference were measured before and 12 months after metformin treatment. Serum concentrations of sex steroids, gonadotropins, and lipids were also assessed. Homeostasis model assessment (HOMA) index and quantitative sensitivity check (QUICKI) index scores were calculated before metformin treatment and after 12 months of use. Results After 12 months of metformin treatment, female patients had significant reduction in weight, BMI, and waist circumference after adjusting for age. Metformin use for 12 months resulted in significant reduction in mean fasting blood glucose and HbA1c in females only. Total cholesterol decreased significantly among men only and serum HDL-C showed a significant rise among females only. Serum LDL-C and triglycerides did not change significantly in females and males. Our study did now significant changes in ACTH and cortisol levels in both females and males after metformin treatment. Metformin use resulted in significant increase in luteinizing hormone (LH) and progesterone levels in males, while it was associated with significant increase in prolactin, follicular stimulating hormone (FSH), and dehydroepiandrostenedione-sulphate (DHEA-S) levels and significant decrease in total testosterone level in females. Conclusion Metformin treatment in females with prediabetes reduces BMI, waist circumference, fasting blood glucose, and HbA1c. The changes in the studied parameters differed significantly according to sex.

Effect of bariatric surgery on endogenous sex hormones and sexhormone-binding globulin levels: a systematic review and meta-analysis.

Most studies have shown beneficial effect of bariatric surgery (BS) on serum levels of sex hormones. A systematic review and meta-analysis was conducted to examine the magnitude of possible changes in levels of sex hormones following BS. Electronic databases were searched, including PubMed, Scopus, Web of Science, and Embase, for relevant studies. The heterogeneity of the studies was examined by χ2 tests and the degree of heterogeneity was estimated using I2 statistic. The results of pooled analyses revealed that BS caused a significant increase in luteinizing hormone (LH), follicular stimulating hormone (FSH), total testosterone (TT), and sex hormone binding globulin (SHBG) levels and conversely, decreased dehydroepiandrosterone (DHEA) and estradiol (E2) levels in males. For females, BS significantly increased LH, FSH, and SHBG levels and conversely, decreased androstenedione (AE), E2 and TT levels. Additionally, the level of progesterone (P), prolactin (PRL), free testosterone (FT) and dehydroepiandrosterone sulfate (DHEA-S) showed no significant changes in patients who had undergone BS. BS changed most sex hormones levels including LH, FSH, TT, SHBG, AE, DHEA, and E2. It seems that BS is able to exert substantial impacts on sex hormones levels and as well as sexual function, however, larger, and more precise trials are required to specifically focus on these claims.

Ethanolic extract of propolis and vitamin E attenuates metal-induced testicular necrosis: time-related study on male reproductive system in albino mice

This study was designed to investigate the protective effects of propolis and vitamin E against time-related metal (aluminum chloride)-induced toxicity on the male reproductive system in albino mice (n = 63). Animals were randomly divided into seven groups (n = 9 each). Group I (control) received 0.9% saline solution; group II was given 50 mg/kg of aluminum chloride (AlCl3); groups III and IV were administered vitamin E (150 mg/kg) and propolis (50 mg/kg), respectively; and groups V, VI and VII were administered AlCl3 + vitamin E, AlCl3 + propolis, and AlCl3 + vitamin E + propolis, respectively, for 45 days. Animals were sacrificed; blood and tissue samples were collected (thrice; fortnightly) for the estimation of hormones i.e., Follicle stimulating hormone (FSH), Luteinizing hormone (LH) and testosterone using Enzyme linked immunosorbent assay (ELISA). Testicular histology, testicular weight, sperm count and motility were estimated. Group II revealed a highly significant decrease in LH, FSH, testosterone, testis weight, sperm count and motility. Groups III–VII showed a significant increase in LH, FSH, testosterone, organ weight, sperm count and motility in the 3rd sampling, as compared to group II. Hence, it is concluded that vitamin E and propolis, acting individually as well as synergistically, mitigate metal-induced time-related toxicity on the reproductive system and testicular histology of male mice.

Serum level evaluation of interleukin-18 in obese women with polycystic ovary syndrome

This study is designed to measure the level of interleukin (IL) 18 in polycystic ovary women and its association with obesity. In this study, blood samples from 50 women with PCOS and 30 healthy control women were collected from AL-Yarmouk Teaching, Baghdad Teaching hospitals During January 2018 - March 2018 for estimation of their serum level of IL18 by using enzyme-linked immunosorbent assay (ELISA) technique and evaluation serum levels of luteinizing hormone (LH), Follicle-stimulating hormone (FSH), Testosterone, prolactin (PRL) and Estradiol (E2) by using Electrochemiluminescence immunoassay (ECLIA). The results showed that there is a highly significant increase (P < 0.001) in serum level of IL18 in PCOS women than in healthy control group. As well as, the results of IL-18 value according to Body mass index (BMI) showed significant difference (P<0.05) between BMI and IL-18 level in all the PCOS patient subgroups (normal weight, overweight and obesity). Also, there was a significant increase in LH, FSH, PRL and T, and significant decrease in E2 was detected in PCOS patients.

Hypothalamic-Pituitary-Ovarian Axis Reactivation by Kisspeptin-10 in Hyperprolactinemic Women With Chronic Amenorrhea.

Context:Hyperprolactinemia-induced hypogonadotropic amenorrhea (hPRL-HA) is a major cause of hypothalamic gonadotrophin-releasing hormone (GnRH) deficiency in women. In hyperprolactinemic mice, we previously demonstrated that hypothalamic kisspeptin (Kp) expression was diminished and that Kp administration restored hypothalamic GnRH release, gonadotropin secretion, and ovarian cyclicity, suggesting that Kp neurons could also play a role in hPRL-HA.Objective:To study the effect of Kp-10 on the gonadotropic-ovarian axis in women with hPRL-HA.Patients:Two women (32 and 36 years old) with chronic hPRL-HA (prolactin: between 94 and 102 and 98 and 112 ng/mL, respectively) caused by cabergoline-resistant microprolactinomas.Interventions:Cabergoline was discontinued 6 months before inclusion. Blood samples were taken every 10 minutes for 12 hours during 2 consecutive days to evaluate luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion. Serum estradiol (E2), testosterone (T), and inhibin B (IB) levels were also measured. Vehicle or Kp-10 (1.5 μg/kg/h) was infused intravenously for 12 hours.Results:Kp-10 induced a significant increase in LH and FSH levels and increased LH pulses. E2, T, and IB serum levels were also significantly increased.Conclusions:In this exploratory study, we demonstrated that administration of Kp-10 reactivated gonadotropin secretion in women with hPRL-HA and increased ovarian activity. Our data suggest that, as in rodents, GnRH deficiency in hPRL-HA is also mediated by an impairment of hypothalamic Kp secretion. Kp-10 or its analogues could have therapeutic application as an alternative approach to restore ovarian function and fertility in women with hPRL-HA resistant to dopamine agonists and in whom pituitary surgery is not possible.

Physiological and Histological Study for the Effect of Escalation Doses of Dostinex (Caprigoline) on Male Mice through Some Biochemical Parameters

Although the history of many drugs proved some beneficial effects, yet uncontrolled use may have serious impact on health especially vital organs as liver and kidney and endocrine glands. Dopamine agonists are the treatment of choice for the majority of patients with hyperprolactinemic disorders. Bromocriptine has been used over the past 30 years, whereas cabergoline has become a first-choice agonist in recent years. The present study was aimed to evaluate the physiological and histological effects of escalated doses of the drug (Caprigoline) in male mice. The experiment includes 40 mice divided on 4 groups. Group 1 treated with PBS represents the control. The groups (2, 3, and 4) treated with the doses (0.5, 5, and 10) mg of caprigoline /Kg body weight respectively. Regarding hormonal assay, the results showed significant (P&lt;0.05) differences between the treated groups and the control. There was a significant increase in luteinizing hormone (LH), testosterone, Triiodothyronine (T3) and Throxine (T4) level accompanies the increase in caprigoline dose. In contrast the Follicle stimulating hormone (FSH) and prolactin (PRL) show a decrease in their levels as the dose become higher. Furthermore; there was a significant increase in level of Alanin aminotransaminase (ALT) as an indicator of liver function and a significant increase in level of urea as an indicator of kidney function in the treated groups compared with the control. The histological study reveal an obvious morphological changes compared with the normal state in the animals treated with the high dose. The liver in mice treated with (5 and 10) mg caprigoline showing focal area of necrosis with inflammatory cells. The kidney in mice treated with 10 mg caprigoline shows a degenerative changes and necrosis of epithelial of micro tubules and thyroidization phenomeno.&#x0D;

Concentración de hormona luteinizante en el suero de la mujer normal

Se ha determinado lo concentración de hormona luteinizante (LH) en el suero sanguíneo de 20 mujeres en edad reproductiva, con ciclos menstruales normales, sin tratamiento hormonal alguno, únicamente a 6 se había implantado un D. l. U. Con este objeto se empleó una técnica radioinmunológica. En tres ciclos no se pudo demostrar una elevación significativa de LH en la mitad del mismo. En los 17 ciclos, considerados bifásicos, ovulatorios, se encontró una concentración mayor de LH en la fase folicular (8 .93 mU/ml, expresados en unidades del 2nd. IRP-HMG) que en la fase luteal (7.43 mU/ml), p = 0.025. Para una duración promedio de 30 días, el pico ovulatorio de LH se presentó alrededor del 17° día del ciclo, con amplias variaciones entre el 11° y el 25° día. La fase luteal duró como término medio 14 días. Lo concentración promedio de LH del pico mesocíclico fue de 79.97 mU/ml, lo cual representó un incremento mayor de nueve veces la concentración de LH hallado durante lo fase folicular.

Efficacy of a Novel Fenugreek Seed Extract (Trigonella foenum-graecum, Furocyst) in Polycystic Ovary Syndrome (PCOS).

Polycystic ovary syndrome (PCOS) is one of the most prevalent hormonal disorders among women of reproductive age causing irregular menstrual cycles, excessive body or facial hair, miscarriage and infertility. The latter being a most common PCOS symptoms. Because the symptoms are seemingly unrelated to one another, PCOS is often overlooked and undiagnosed. The present study is an open label, one-arm, non-randomized, post-marketing surveillance study in 50 premenopausal women (18-45 years, BMI<42) diagnosed with PCOS using a novel Trigonella foenum-graecum seed extract (fenugreek seed extract, Furocyst, 2 capsules of 500 mg each/day) extract, enriched in approximately 40% furostanolic saponins, over a period of 90 consecutive days. The study was conducted to determine its efficacy on the reduction of ovarian volume and the number of ovarian cysts. Ethical committee approval was obtained for this study. Furocyst treatment caused significant reduction in ovary volume. Approximately 46% of study population showed reduction in cyst size, while 36% of subjects showed complete dissolution of cyst. It is important to mention that 71% of subjects reported the return of regular menstrual cycle on completion of the treatment and 12% of subjects subsequently became pregnant. Overall, 94% of patients benefitted from the regimen. Significant increases in luteinizing hormone (LH) and follicular stimulating hormone (FSH) levels were observed compared to the baseline values. Extensive blood chemistry, hematological and biochemical assays demonstrated the broad-spectrum safety. Furocyst caused significant decrease in both ovarian volume and the number of ovarian cysts. Serum ALT, BUN and CK were assessed to demonstrate the broad-spectrum safety of Furocyst. No significant adverse effects were observed. In summary, Furocyst was efficacious in ameliorating the symptoms of PCOS.

The pituitary-Leydig cell axis before and after orchiectomy in patients with stage I testicular cancer

IntroductionThis study investigates the pituitary-Leydig cell axis in patients with stage I testicular germ cell cancer (TGCC) followed with surveillance only, in order to evaluate the risk of Leydig cell dysfunction one year after orchiectomy. Patients and methodsA retrospective evaluation of reproductive hormones in patients with unilateral stage I TGCC (N=72) without relapse diagnosed between 1990 and 2008. A group of healthy males (N=706) served as controls. ResultsBefore orchiectomy there were no significant differences in luteinizing hormone (LH) and testosterone (T) levels between human chorionic gonadotropin (hCG)-negative patients and controls, although 33% of the patients were outside the 97.5 percentile when using bivariate LH/T evaluation. At 1-year follow-up there was a significant increase in LH (ΔLH=2.04IU/L, p<0.001), and 57% of the patients had an LH/T relation outside the 97.5 percentile. ConclusionPatients with stage I TGCC are at increased risk of having an LH/T relation outside the normal range one year after orchiectomy, suggesting insufficient Leydig-cell function. Whether a proportion of these patients will develop manifest hypogonadism and benefit from androgen therapy is yet to be clarified.

Response to exogenous kisspeptin varies according to sex and reproductive condition in Siberian hamsters ( Phodopus sungorus)

Most animals experience marked changes in reproductive status across development that are regulated by changes in the hypothalamo–pituitary–gonadal (HPG) axis. The upstream mechanisms regulating this axis remain less well understood. The neuropeptide kisspeptin serves as a positive regulator of reproduction; the precise actions of kisspeptin on the HPG axis in animals of differing developmental and seasonal reproductive states, however, remain unresolved. Further, sex differences in response to kisspeptin have not been fully explored. In Experiment 1, we investigated whether sensitivity to a broad range of kisspeptin doses differed in adult male and female Siberian hamsters held on reproductively inhibitory or stimulatory photoperiods. In Experiment 2, we asked whether the response to kisspeptin differed across stages of reproductive development. Males and females displayed elevated luteinizing hormone (LH) in response to kisspeptin; however, the sexes differed in this response, with males showing greater LH responses to kisspeptin than females. Hamsters responded to kisspeptin across all stages of reproductive development, although the magnitude of this response differed between animals of differental ages and between the sexes. Males showed significant increases in LH at an earlier developmental age than females; females also showed blunted LH responses during early adulthood whereas males remained relatively constant in their response to kisspeptin. These findings suggest that reproductively active and inactive hamsters are responsive to kisspeptin, but that the sexes differ in their responsiveness. Collectively, these data provide further insight into the basic actions of kisspeptin in the regulation of reproduction and provide a potential mechanism for the regulation of differential reproductive responses between the sexes.

Weak evidence of bright light effects on human LH and FSH

BackgroundMost mammals are seasonal breeders whose gonads grow to anticipate reproduction in the spring and summer. As day length increases, secretion increases for two gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH). This response is largely controlled by light. Light effects on gonadotropins are mediated through effects on the suprachiasmatic nucleus and responses of the circadian system. There is some evidence that seasonal breeding in humans is regulated by similar mechanisms, and that light stimulates LH secretion, but primate responses seem complex.MethodsTo gain further information on effects of bright light on LH and FSH secretion in humans, we analyzed urine samples collected in three experiments conducted for other goals. First, volunteers ages 18-30 years and 60-75 commenced an ultra-short 90-min sleep-wake cycle, during which they were exposed to 3000 lux light for 3 hours at balanced times of day, repeated for 3 days. Urine samples were assayed to explore any LH phase response curve. Second, depressed participants 60-79 years of age were treated with bright light or dim placebo light for 28 days, with measurements of urinary LH and FSH before and after treatment. Third, women of ages 20-45 years with premenstrual dysphoric disorder (PMDD) were treated to one 3-hour exposure of morning light, measuring LH and FSH in urine before and after the treatments.ResultsTwo of the three studies showed significant increases in LH after light treatment, and FSH also tended to increase, but there were no significant contrasts with parallel placebo treatments and no significant time-of-day treatment effects.ConclusionsThese results gave some support for the hypothesis that bright light may augment LH secretion. Longer-duration studies may be needed to clarify the effects of light on human LH and FSH.

Photoperiodic response curves for plasma LH concentrations and age at first egg in female broiler breeders

The objective of this work was to define precisely the response curve for photoinduced luteinizing hormone (LH) release in feed-restricted meat-type (broiler) breeder females and to compare it with the photoperiodic response curve for advance in age at first egg (AFE). Birds with a mean body weight of 2.0 kg at 20 weeks of age were transferred from an 8 to a 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 14 or 18-h photoperiod; change in plasma LH was measured 4 d after photostimulation and subsequent individual AFE recorded. The first significant increase in LH secretion was seen in birds transferred to an 11.5-h photoperiod, but no further significant increases in LH were observed in birds transferred to longer photoperiods. A photoperiodic response curve based on a meta-analysis of changes in photoinduced LH secretion observed in this study and data from an earlier experiment using dwarf broiler breeders indicated a critical daylength of about 9.5 h and a saturation daylength of approximately 13 h. Similarly, the first significant advance in AFE occurred in birds transferred to an 11-h photoperiod, but with no further significant increases seen in birds transferred to photoperiods >11 h. A response curve for photoinduced advances in AFE was produced by meta-analysis using data from the present study and from an earlier investigation involving fewer, more widely spaced photoperiods. It is concluded, in female broiler breeders, that the photoperiodic response curves for photoinduced LH release and AFE are similar, with the point at which the responses begin to rise steeply (classical critical daylength) occurring at 9.5 h and the asymptote (classical saturation daylength) at 13 h. Functionally, however, the minimum photoperiod to achieve a significant change in either LH secretion or advance in AFE is between 11 and 11.5 h.

In vivo and in vitro anti-androgenic effects of DE-71, a commercial polybrominated diphenyl ether (PBDE) mixture

PBDEs have been synthesized in large quantities as flame retardants for commercial products, such as electronic equipment and textiles. The rising in levels of PBDEs in tissues in wildlife species and in human milk and plasma samples over the past several years have raised concerns about possible health effects. Recently, we showed that the PBDE mixture, DE-71, delayed puberty and suppressed the growth of androgen-dependent tissues in male Wistar rat following a peri-pubertal exposure. These effects suggested that DE-71 may be either inducing steroid hormone metabolism or acting as an androgen receptor (AR) antagonist. To elucidate the potential anti-androgenic effects of this mixture, we evaluated DE-71 in several in vivo assays, which are responsive to alterations in androgen activity. In a pubertal exposure study designed to further evaluate the delay in preputial separation (PPS), we observed a dose-dependent delay in PPS with 60 and 120 mg/kg/day of DE-71 (4 and 5 days) and a corresponding suppression of ventral prostate (VP) and seminal vesicle growth at both doses. Adult males exposed to 60 mg/kg DE-71 for 3 days resulted in a significant increase in luteinizing hormone and a non-significant increase in testosterone, androstenedione and estrone. DE-71 also tested positive for anti-androgenic activity in an immature rat Hershberger assay, with decreases in mean VP and seminal vesicle weight following doses of 30–240 mg/kg. DE-71 and the individual BDE congeners which comprise the mixture (BDE-47, -99, -100, -153, -154) were also evaluated in vitro. First, AR binding was evaluated in a competitive binding assay using rat VP cytosol. In addition, we evaluated gene activation in a transcriptional activation assay using the MDA-kb2 cell line which contains an endogenous human AR and a transfected luciferase reporter. DE-71 and BDE-100 (2, 4, 6-pentaBDE) both inhibited AR binding, with IC50s of approximately 5 μM. In addition, DE-71 and two of the congeners (BDE-100 and BDE-47) inhibited DHT-induced transcriptional activation. The pattern of inhibition shown in the double-reciprocal plot for BDE-100 and the linear slope replot confirmed that the in vitro mechanism is pure competitive inhibition, with a inhibition constant ( K i) of 1 μM. The delay in puberty in the male rat and decreased growth of androgen-dependent tissues observed previously following exposure to DE-71 were likely due to this inhibition of AR binding by several of the congeners which make up this mixture.

Ovarian steroid hormone modulation of the acute effects of cocaine on luteinizing hormone and prolactin levels in ovariectomized rhesus monkeys.

Cocaine stimulates significant increases in luteinizing hormone (LH) and decreases prolactin levels in gonadally intact rhesus monkeys, but cocaine did not alter plasma levels of these anterior pituitary hormones in ovariectomized females. These findings suggested that ovarian steroid hormones may contribute to the endocrine effects of acute cocaine administration. To test this hypothesis, the acute effects of cocaine and placebo-cocaine on plasma LH and prolactin levels were examined in five ovariectomized rhesus females during three chronic hormone replacement conditions: 1) estradiol (E2beta) treatment (0.0015-0.006 mg/kg/day i.m.), 2) progesterone treatment (0.32 mg/kg/day i.m.), and 3) combinations of progesterone (0.32 mg/kg/day i.m.) and E2beta (0.002 and 0.004 mg/kg/day i.m.). Cocaine (0.8 mg/kg i.v.) did not alter prolactin or LH in ovariectomized monkeys without ovarian steroid replacement. During chronic estradiol treatment, cocaine produced an estradiol dose-dependent decrease in prolactin. Cocaine also decreased prolactin during treatment with progesterone alone and progesterone + E2beta (0.004 mg/kg/day i.m.). Cocaine stimulated a significant increase in LH during treatment with progesterone alone, but not during treatment with progesterone + E2beta, or three of four estradiol treatment doses. Cocaine pharmacokinetics did not differ as a function of hormone replacement conditions. Together, these data suggest that both E2beta and progesterone modulate cocaine's effects on prolactin, whereas E2beta alone and in combination with progesterone, do not facilitate LH release in response to cocaine in ovariectomized rhesus females.

Clomiphene increases free testosterone levels in men with both secondary hypogonadism and erectile dysfunction: who does and does not benefit?

Secondary hypogonadism is more common than primary gonadal failure and is seen in chronic and acute illnesses. Although testosterone has a role in erections, its importance in erectile dysfunction (ED) has been controversial. Hypogonadism produced by functional suppression of pituitary gonadotropins has been shown to correct with clomiphene citrate, but with a modest effect on sexual function. We wondered if longer treatment would produce improved results. A total of 178 men with secondary hypogonadism and ED received clomiphene citrate for 4 months. Sexual function improved in 75%, with no change in 25%, while significant increases in luteinizing hormone (P<0.001) and free testosterone (P<0.001) occurred in all patients. Multivariable analysis showed that responses decreased significantly with aging (P<0.05). Decreased responses also occurred in men with diabetes, hypertension, coronary artery disease, and multiple medication use. Since these conditions are more prevalent with aging, chronic disease may be a more important determinant of sexual dysfunction. Men with anxiety-related disorders responded better to normalization of testosterone. Assessment of androgen status should be accomplished in all men with ED. For those with lower than normal age-matched levels of testosterone treatment directed at normalizing testosterone with clomiphene citrate is a viable alternative to giving androgen supplements.

Elevated luteinizing hormone expression colocalizes with neurons vulnerable to Alzheimer's disease pathology.

In individuals with Alzheimer's disease (AD), there is a two-fold elevation in the serum concentrations of the gonadotropins, luteinizing hormone (LH), and follicle stimulating hormone compared to age-matched controls. Whether this plays a role in disease pathogenesis is unclear. Nonetheless, gonadotropins are known to cross the blood brain barrier and the highest density of gonadotropin receptors in the brain are found within the hippocampus. We report for the first time the localization of LH in the cytoplasm of pyramidal neurons. In addition, we find a significant increase in LH in the cytoplasm of pyramidal neurons and neurofibrillary tangles of AD brain compared to age-matched control brain. Whereas the functional consequences of increased neuronal LH are unknown, it is notable that LH is primarily localized to those neurons that are known to be vulnerable to Alzheimer's disease-related neurodegeneration. Elevated serum and cortical neuron levels of LH, coupled with the decline in sex steroid production, could play important roles in the pathogenesis of AD.

Reproduction: Effect of GNRH and HCG administration on plasma LH and testosterone concentrations in normal stallions, aged stallions and stallions with lack of libido

Summary Gonadotrophin‐releasing hormone (GnRH) (a single intravenous injection with 0.042 mg busereline acetate) was administered to control stallions (n=5), aged stallions (n=5) and stallions with lack of libido (n=5). Jugular blood samples were taken at ‐10, 0, 10, 20, 40 and 80 minutes after treatment and measured for luteinizing hormone (LH) and testosterone concentrations. A single intravenous injection of hCG (3000 IE) was given 1 day later. Venous blood samples were taken at ‐60, 0, 15, 30, 60, 120, and 240 minutes after treatment and measured for the testosterone concentration. The experiment was performed in the breeding season. There was a wide variation between stallions in basal concentrations of LH and testosterone. The treatment groups all showed a significant increase in LH and testosterone concentrations after treatment with GnRH. There was a significant difference (P<0.05) between the control, the lack of libido stallions and the aged stallions in the production of LH before and after stimulation with GnRH. The aged stallions had higher basal LH concentrations. GnRH induced a rise in plasma LH in all groups, but the greatest response was observed in aged stallions. No response to GnRH was seen with respect to plasma testosterone. There was an increase in plasma testosterone following hCG; however, this increase was very small in aged stallions. After stimulation with hCG the control and lack of libido stallions had a significant increase (P<0.05) in testosterone production. In conclusion, stimulation with either GnRH or hCG can be a valuable method to test whether the function of the stallion's reproductive endocrine system is optimal.

The Effects of a Single Long Photoperiod on Induction and Dissipation of Reproductive Photorefractoriness in European Starlings

In many birds, long photoperiods stimulate gonadal maturation but also cause photorefractoriness, leading to gonadal regression. While much is known about the neuroendocrinology of photostimulation, little is known about photorefractoriness, partly due to lack of an experimental model. This study aimed to develop a model to test whether a single long photoperiod (LP) initiates the mechanism leading to photorefractoriness. It made use of the fact that in castrated European starlings, luteinizing hormone (LH) is low in photorefractory birds and high in photosensitive birds. In the first experiment, groups of castrated photorefractory birds were transferred from a long to a short photoperiod and then exposed to one LP every 5, 10, 20, 30, 40, or 60 days. In birds exposed to one LP every 5 days, LH stayed low. In birds exposed to one LP every 10 days, each LP caused a pulse in LH, but mean LH remained low. One LP every 20 days increased LH 6 days later, followed by a decrease at 11 days and then a further increase, so that overall, LH increased slowly. In birds exposed to one LP every 30, 40, or 60 days, LH increased at the same rate as in short photoperiod controls. Each LP did not cause a significant increase in LH, but did cause a decrease. A second experiment examined the changes in LH following a LP in more detail. Castrated starlings had been exposed to one LP every 14 days for 16 weeks. On the day of the final LP, LH values were midway between photorefractory and photosensitive values. The LP caused an increase in LH from the second day to a peak after 7 days. Thereafter, LH declined to initial values after 14 days, followed, in the absence of further LP, by a second increase to photosensitive values. These results suggest that the mechanisms causing photostimulation and photorefractoriness are both initiated during the first long photoperiod. That gonadal maturation precedes regression must reflect the relative rates at which the two processes reach completion.