Significant Changes In LH Research Articles

Bitter Taste Receptor Ligand Improves Metabolic and Reproductive Functions in a Murine Model of PCOS.

Polycystic ovary syndrome (PCOS) results from functional ovarian hyperandrogenism due to dysregulation of androgen secretion. Cultured theca cells from polycystic ovaries of women with the most common form of PCOS overexpress most androgen producing enzymes, particularly CYP450c17. In this study, a murine model was used of PCOS induced by chronic feeding with a high-fat diet that exhibits the reproductive, hyperandrogenic, and metabolic constellation of PCOS symptoms seen in women. Oral administration of KDT501, a hops-derived bitter taste receptor (Tas2R 108) isohumulone ligand resulted in resolution of PCOS-associated endocrine and metabolic disturbances and restored reproductive function. Pioglitazone, a PPARγ agonist, also improved metabolic and reproductive function, though not to the same degree as KDT501. Specifically, treatment of the murine PCOS model with KDT501 resulted in reduced testosterone and androstenedione levels in the absence of significant changes in LH or FSH, improved glucose tolerance and lipid metabolism, and reduced hepatic lipid infiltration and adiposity. There was significant improvement in estrous cyclicity and an increase in the number of ovarian corpora lutea, indicative of improved reproductive function after exposure to KDT501. Finally, ex vivo exposure of murine ovaries to KDT501 attenuated androgen production and ovarian expression of CYP450c17. Interestingly, the ovaries expressed Tas2R 108, suggesting a potential regulation of ovarian steroidogenesis through this chemosensory receptor family. In summary, a therapeutic strategy for PCOS possibly could include direct influences on ovarian steroidogenesis that are independent of gonadotrophic hormone regulation.

Effects of I-131 therapy on gonads and pregnancy outcome in patients with thyroid cancer

We examined the effects of I-131 therapy for thyroid cancer on female and male gonads and pregnancy outcome. After an extensive review of the published literature we concluded that ablative administration of I-131 therapy may result in transient abnormalities of ovarian and testicular function, but subsequent pregnancies are safe without any significant consequences to offspring outcome.

Comparison of Simvastatin and Metformin in Treatment of Polycystic Ovary Syndrome: Prospective Randomized Trial

Polycystic ovary syndrome (PCOS) is characterized by ovarian dysfunction and hyperandrogenism; it is also associated with increased cardiovascular risks such as adverse lipid profile and endothelial dysfunction. Metformin and, more recently, statins have been shown to improve endocrine and metabolic aspects of PCOS. The aim of the study was to compare effects of simvastatin and metformin on PCOS. In a prospective trial, women with PCOS (n = 136) were randomized to simvastatin (S), metformin (M), or simvastatin plus metformin (SM) groups. Evaluations were performed at baseline and after 3 months. The study was conducted at an academic medical center. The change of serum total testosterone was measured. The study was completed by 113 subjects. Total testosterone decreased significantly and comparably in all groups: by 17.1, 13.6, and 15.1%, respectively, in the S, M, and SM groups. Significant decreases were also observed in all groups with respect to body mass index, C-reactive protein, and soluble vascular cell adhesion molecule-1. DHEAS declined significantly only in the S group. None of the treatments were associated with significant changes in LH or FSH. Total cholesterol and low-density lipoprotein cholesterol significantly declined only in S and SM groups. Simvastatin treatment was superior to metformin alone, whereas a combination of simvastatin and metformin was not significantly superior to simvastatin alone.

Effects of cocaine–amphetamine regulated transcript (CART) on hormone release

Objective: Cocaine- and amphetamine-regulated transcript (CART) is a recently described neuropeptide widely expressed in the rat brain. CART is abundant in hypothalamus nuclei controlling anterior pituitary function. In the paraventricular nucleus CART mRNA is colocalized with vasopressin and corticotrophin-releasing factor containing neurons. The data may suggest that CART plays a role in hypothalamic regulation of neuroenocrine functions. Material and methods: Male Wistar–Kyoto rats were investigated. Experiment I: CART was administered intracerebroventricularly (i.c.v.) in a dose of 0.5 μg dissolved in 5 μl vehicle. At 60, 120 min after the infusion of CART or vehicle animals were decapitated and trunk blood was collected until hormonal estimations. Experiment II: CART in a dose of 10 μg was injected intravenously (i.v.). At 60, 120, 240 min the rats were decapitated and the trunk blood was collected. Serum rLH, rFSH, rPRL, rTSH, rGH and plasma leptin, NPY concentrations were measured by RIA methods. Results: CART administered centrally (i.c.v.) simulated significantly GH release after 60 min ( p<0.05) and after 120 min ( p<0.01). CART increased also PRL after 60 min ( p<0.05). A marked increase of corticosterone level was observed at 60 and 120 min ( p<0.01, p<0.01). We did not observe significant changes in LH, FSH and TSH. We found an increase of serum leptin concentrations at 60 min after CART administration ( p<0.01). However, serum NPY levels did not change. After intravenous injection (i.v.) of CART an increase of GH was observed at 120, 240 min ( p<0.01, p<0.01, respectively). A rise in serum PRL was found at 240 min ( p<0.05). Corticosterone concentrations were enhanced at 60, 120, 240 min ( p<0.01, p<0.01, p<0.01, respectively). We did not observe significant changes in LH, FSH and TSH. Conclusions: CART may play a modulating role in the mechanism of pituitary hormone release.

Comparison of the effects of ovarian cauterization and gonadotropin-releasing hormone agonist and oral contraceptive therapy combination on endocrine changes in women with polycystic ovary disease

To study the effects of laparoscopic ovarian cauterization and combination of long-acting GnRH agonist (GnRH-a) and oral contraceptive (OC) therapy on endocrine changes in women with clomiphene citrate (CC)- resistant polycystic ovary disease (PCOD). Prospective, randomized. University-based infertility clinic. Seventeen women with CC-resistant PCOD were included randomly in the study to either laparoscopic ovarian cautery or GnRH-a and OC therapy for 3 months. Serum concentrations of LH, FSH, androstenedione (A), T, and sex hormone-binding globulin (SHBG) were determined before each therapeutic approach and during the follicular phase of first menstrual cycle after the cessation of each treatment. The mean serum concentrations and the clinical profiles were similar in both groups. Both groups showed significant changes in LH, FSH, A, T, and SHBG compared with pretreatment levels. There were no significant differences in the final concentrations of LH, FSH, and A between the two study groups after each treatment, whereas T and SHBG levels were significantly different in the goserelin and OC group. The decrease in LH and increase in SHBG serum concentrations were greater in the goserelin and OC-treated women [-59% and + 5.9% versus - 70% and + 13.5%, respectively]. Although the SHBG concentration increased in both groups, the serum SHBG concentration of the goserelin and OC group was significantly higher than the other group. Both therapeutic modalities revealed similar effects on the endocrine profiles in women with CC-resistant PCOD. Considering the invasiveness, cost, and potential complications of laparoscopic ovarian cauterization, noninvasive medical treatment with GnRH-a and OC combination may be more effective in restoring the optimal follicular environment in women with PCOD.

Effects of follicular phase exercise on luteinizing hormone pulse characteristics in sedentary eumenorrhoeic women

Current studies reveal little regarding the inception of exercise-induced LH changes during physical training. This study aimed to assess the susceptibility of the hypothalamic-pituitary axis to the acute physical stress of exercise in untrained, physically inactive women. The acute effects of submaximal endurance exercise upon the pulsatile LH secretion in the follicular phase were compared with those accompanying leisurely strolling for a similar time period. All subjects were eumenorrhoeic, as determined by biphasic temperature patterns, detection of the urinary LH surge, and mid-luteal serum progesterone levels. Subjects were not physically active and had little history of strenuous exercise (VO2max = 38.0 +/- 1.8) (mean +/- SEM) ml/kg/min). All women completed a 13.5-hour pulsatility test which included three consecutive 20-minute runs on a treadmill at 50, 60 and 70% of the subjects' maximum oxygen uptake (n = 16). Six of these same subjects completed a separate test on another occasion in which one hour of leisurely strolling was substituted for exercise. Blood was sampled every 10 minutes via an indwelling cannula for 4.5 hours before and 8 hours after one hour of exercise and or strolling. A pulse algorithm (Pulsar) was used to quantify LH pulse characteristics. Exercise produced no significant effects upon LH pulse frequency or mean serum LH concentration. However, exercise of moderate intensity caused a significant increase in LH pulse amplitude (P < 0.05). Strolling produced no significant changes in LH secretion. Acute exercise of moderate intensity in the follicular phase of untrained women is an insufficient stimulus to inhibit the GnRH pulse generator in the post-exercise period, yet may produce a slight stimulatory effect on the amount of LH released per pulse.

Concentrations of prolactin, LH and FSH after naloxone administration in follicular-phase gilts

Studies were initiated to extend previous data on the pituitary hormone secretion after naloxone (NAL) administration to gilts during the follicular phase. Gilts which had exhibited two previous estrous periods were randomly assigned to treatment with 1 mg naloxone (NAL)/kg b.w. on day 16 ( N = 6) or day 20 ( N = 6) of the estrous cycle ( N = 6). Five additional gilts were treated with 2 mg NAL/kg b.w. on day 16. Control animals received saline alone on day 16 ( N = 6) or day 20 ( N = 6). Peripheral blood samples were collected every 15 min from 2 h prior to 6 h after infusion of NAL or saline. Prolactin, LH and FSH concentrations were determined by RIA procedures. On day 20 of the estrous cycle, prolactin concentration after NAL administration was reduced as compared to the control group for the entire post-treatment period ( P < 0.05). The greatest decrease in prolactin concentration was found during the 5th hour after NAL administration ( P < 0.01). On day 16 of the cycle, NAL at both doses did not influence mean concentration of prolactin. The treatment regimen failed to demonstrate significant changes in LH and FSH concentration after NAL administration on days 16 and 20 of the cycle. The results suggest that prolactin secretion is modulated by endogenous opioid peptides during the late follicular phase.

Effects of photoperiod on hibernation in castrated Turkish hamsters.

Hibernation and circulating reproductive hormones [luteinizing hormone, follicle-stimulating hormone, and prolactin (LH, FSH, and PRL)] were studied for greater than 40 wk in castrated male Turkish hamsters (Mesocricetus brandti) housed in either a long-day cold or short-day cold environment. A significantly greater percentage of short-day animals hibernated than did long-day animals, indicating that short-day exposure can predispose Turkish hamsters to enter hibernation and that this photoperiodic effect cannot be explained entirely by the inhibitory influence of short days on testicular endocrine activity. Long-day castrates showed no significant changes in LH or FSH levels during the experiment. In the short-day castrates serum LH, FSH, and PRL levels were reduced after 4-9 wk and increased again after 18-23 wk of short-day exposure. The hibernation season ended after 30-34 wk on short days, several weeks later than in testis-intact males studied previously. These results indicate that gonadal factors are not required for the termination of hibernation but may influence its timing. The resumption of FSH secretion occurred no later during short-day exposure in castrated hibernators than in the preceding study of testis-intact, short-day males hibernating in the cold or those held at room temperature. Thus the endogenous timing mechanism regulating the reactivation of the hypothalamopituitary axis toward the end of the winter season is apparently gonad independent and is little affected by the low body temperatures experienced during hibernation.

The effects of estrogen and progestin on endogenous opioid activity in oophorectomized women.

Sex steroids may modulate the secretion of beta-endorphin (beta-EP). Naloxone (Nal), an opioid antagonist, has been used as a probe of central opioid activity. Nal-evoked responses of PRL and LH were evaluated in the midluteal (ML) and late follicular (LF) phases of ovulatory women (Pre) and compared to responses of oophorectomized women before and after the administration of conjugated estrogens (CE) and again after CE and progestin administration. In the ML and LF phases, serum LH increased significantly (P less than 0.05 and P less than 0.01, respectively) during Nal infusion for 4 h, while PRL did not change. In oophorectomized women, there were no significant changes in LH or PRL during Nal infusion. After 3 weeks of CE treatment (1.25 mg daily), LH increased during Nal infusion (P less than 0.05), as did PRL (P less than 0.01). After treatment with CE and medroxyprogesterone acetate (MPA), LH and PRL both increased (P less than 0.05 and P less than 0.01, respectively). The area under the LH curve during Nal infusion after CE and MPA treatment was greater than that after CE alone. Both of these responses were comparable to those of the LF and ML phases of Pre women. During Nal infusion, LH pulse frequency increased in the ML compared to the LF phase of the cycle and, in oophorectomized women, was greater after CE and CE with MPA treatment compared to pretreatment values (P less than 0.05). LH amplitudes during Nal infusion were highest in the ML phase and after CE and MPA treatment in oophorectomized women, and these LH amplitudes were similar. No correlation was found between peripheral plasma beta-EP and Nal-evoked LH responses. No differences were evident in plasma beta-EP levels between Pre and oophorectomized women. In conclusion, 1) endogenous opioid activity is low in oophorectomized women; 2) treatment with estrogen increases opioid activity, and the addition of a progestin increases this activity further; and 3) these data support the contention that sex steroids exert a profound influence on endogenous opioid activity.

Inhibition of serum luteinizing hormone and testosterone with an inhibitory analog of luteinizing hormone-releasing hormone in adult male rhesus monkeys.

The effects of single and repeated administration of a potent LHRH inhibitory analog (antagonist) [( N-acetyl-D-p-chloro-Phe1,2,D-Trp3,D-Arg6,D-Ala10]LHRH) on serum concentrations of LH and testosterone (T) in adult rhesus monkeys were studied. In Exp 1, single sc injections of the LHRH antagonist (400 micrograms and 50 micrograms) or vehicle were administered and the temporal changes in serum LH and T were determined (n = 4 per group). Both LH and T declined markedly in all animals as soon as 30 min after the LHRH antagonist injection, reaching the nadir (80%) approximately 8 h later and remaining significantly lower than baseline levels for up to 24 h. Control animals had no marked variations in either LH or T serum levels. In Exp 2, daily sc injections of different doses of LHRH antagonist (400 micrograms, 50 micrograms, and 10 micrograms) or vehicle were administered for 7 days to four animals in each group. The animals in the control group had no significant changes in LH or T levels, whereas those treated with the lowest dose of LHRH antagonist (10 micrograms) had decreased T levels in the absence of changes in LH. The other two doses of LHRH antagonist (400 micrograms and 50 micrograms) induced, as early as 8 h after the initial injection, dramatic decreases in serum levels of both LH and T and these values remained significantly lower than control for up to 3 and 4 days after discontinuation of drug administration, respectively. We conclude from this study that LHRH inhibitory analogs are potent inhibitors of LH and T in adult rhesus monkeys. They have potential use in clinical trials for male contraception as well as in patients in whom inhibition of gonadotropin and steroid secretion is desired.

The hemicastrated rat: definition of a model for the study of the regulation of testicular steroidogenesis.

A comprehensive study has been made of the hemicastrated rat from 2 to 12 months of age in order to define what might represent an ideal model in which to study testicular regulation. Although there was no compensatory hypertrophy in the remaining testis of the mature hemicastrated rat, levels of plasma testosterone fell significantly within 4 h after surgery in all age groups older than 3 months, and were restored to normal levels almost immediately, usually within 8 h. There were no significant changes in LH and prolactin, and the significant rise in FSH was sufficiently delayed (2 days or more) to suggest that none of these three hormones was implicated in any obvious way in the compensatory restoration of plasma testosterone levels. Although a single testis was capable of maintaining normal plasma testosterone concentrations, its response to human chorionic gonadotrophin at 24 h after hemicastration was significantly less than that of intact animals, suggesting that the single testis was functioning at near-maximal capacity. The hormonal responses to repetitive blood sampling and to sham-surgery simulated the response to hemicastration remarkably. However, these responses were never statistically significant in within-group analysis, and therefore did not obscure the significant fall of plasma testosterone levels in response to hemicastration. The basic mechanism by which plasma testosterone is restored in the hemicastrated rat is still unknown, but the options have been narrowed.

Rabbit follicular adenylyl cyclase activity. II. Gonadotropin-induced desensitization in granulosa cells and follicle shells.

Previous studies reported a simultaneous decline in luteinizing hormone (LFI)- and follicle stimulating hormone(FSH)-stimulated adenylyl cyclase (AC) activities in rabbit follicles exposed in vivo to a coital-induced surge of LH or a bolus of human chorionic gonadotropin (hCG) (HunzickerDunn and Birnbaumer, 1976). In these studies, FSH-stimulable AC activity was measured using an FSH preparation which contained “.‘l% LH (Reichert and Wilhelrni, 1973). In an effort to evaluate more precisely the role of FSH in follicular function in rabbits, AC activity has been reevaluated using a highly purified fraction of FSH to measure FSH-stimulated AC activity. LH- and FSHstimulable AC activities were measured both in rabbit follicular granulosa cells and in thecal cell-predominated follicle shells at various times after mating or the injection of an ovulatory concentration of hCG. In follicle shells, LH-stimulated AC rapidly fell during the first hour after mating or hCG injection while FSH-stimulated AC did not change. Both AC parameters declined to near basal levels by 7 h. The rate of AC desensitization was markedly different in granulosa cells. No significant changes in LH- or FSH-stimulated AC activities occurred during the first 2 h following either the endogenous surge of LH or the exogenous bolus of hCG, but by 4.5 h gonadotropin-stimulated AC activities were significantly (P<0.001) reduced. However, when isolated granulosa cells were exposed in vitro for 60 mm to either LU or FSH, both the homologous and the heterologous gonadorropin-stimulated AC activities, respectively, were reduced by 50%. These results demonstrate different rates of AC desensitization in follicle shells to LH and FSH when a purified fraction of FSH is used to measure FSH-stimulated AC activity. They also reveal markedly different rates of AC desensitization to gonadotropins in vivo between granulosa cells and thecal shells. Indirect evidence suggests that the retarded rate of AC desensitization in granuloss cells may be attributable to the avascularity of this follicular compartment.