Mean Luteinizing Hormone Research Articles

Luteinizing hormone (LH) levels in male workers exposed to urban stressors

The aim of the study is to evaluate if occupational exposure to urban stressors could cause alterations in luteinizing hormone (LH) plasma levels in male traffic policemen vs. administrative staff of Municipal Police. After excluding the subjects with the main confounding factors, male traffic police and administrative staff of Municipal Police were matched by age, working life, body mass index (BMI), alcohol drinking habit, cigarette smoking habit and habitual consumption of Italian coffee. In 166 male traffic police mean LH values were significantly higher compared to 166 male administrative employees. The distribution of LH values in traffic police and in administrative employees was statistically significant. Our results suggest that recent exposure to urban stressors (chemical, physical and psycho-social) can alter the plasma concentration of LH. In agreement with our previous research, levels of plasma LH may be used as early biological markers, valuable for the group, used in occupational set before the appearance of the disease.

Can audio–visual or visual stimuli from a prospective mate stimulate a reproductive neuroendocrine response in sheep?

Stimuli from a prospective mate increase the secretion of luteinising hormone (LH) in sheep. This ‘male effect’ in ewes and ‘female effect’ effect in rams is predominantly mediated by olfactory signals, though it is thought that non-olfactory signals play synergistic or substitutive roles. In this study, we tested whether exposure to visual or audio–visual stimuli from a prospective mate would stimulate an increase in LH secretion in ewes (Experiment 1) and rams (Experiment 2). In Experiment 1, groups of eight Merino ewes were exposed to one of three stimuli midway through a frequent blood-sampling regimen: full ram contact, still images of rams, a video of ewes and rams mating. Control ewes (n = 8) were completely isolated from rams. Exposure to still images of rams appeared to stimulate an increase in mean LH concentrations (P < 0.05) and tended to increase LH pulse frequency (P < 0.1), but the response was significantly smaller than that observed in ewes exposed to rams (P < 0.01). Audio–visual stimuli had no effect on any parameters of LH secretion (P > 0.1). In Experiment 2, Merino rams were allocated to either an Exposure (n = 7) or a Control (n = 7) group. Exposure rams underwent two exposure periods midway through a frequent blood-sampling regimen; exposure to still images of ewes and audio recorded during mating of ewes and rams (audio–visual exposure); exposure to oestrous ewes (ewe exposure). Control rams were sampled at the same frequency but remained isolated from ewe stimuli. Exposure of rams to the audio–visual stimuli did not affect any parameters of LH secretion (P > 0.1). In contrast, exposure to oestrous ewes increased LH pulse frequency (P < 0.05) and advanced the onset of the next LH pulse (P < 0.05). In conclusion, visual signals appear to be involved in eliciting the neuroendocrine response of ewes to rams and are of greater importance to this phenomenon in ewes (male effect) than rams (female effect). However, overall the visual and audio–visual signals used in this study were far less effective than stimulus animals, suggesting that these stimuli are less important than olfactory signals, or a combination of olfactory and audio–visual signals.

Alterations in Hormone Levels After Adjuvant Chemoradiation in Male Rectal Cancer Patients

To evaluate follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels after postoperative chemoradiation in men with rectal cancer. Forty-three men with rectal cancer had baseline and postchemoradiation FSH, LH, and testosterone measured. Adjuvant chemoradiation consisted of two 5-day cycles of bolus 5-fluorouracil (5-FU) every 4 weeks at a dose of 500 mg/m(2)/d followed by concurrent chemoradiation followed by two additional 5-day cycles of 5-FU at a dose of 450 mg/m(2)/d. Continuous-infusion 5-FU at 225 mg/m(2)/d was given during radiation. Pelvic radiation consisted of a three- or four-field technique with a median dose of 54.0 Gy in 30 fractions. Median follow-up was 6.1 years. Mean baseline FSH levels increased from 5.3 to a peak of 23.9 IU/L (p < 0.001) 13-24 months after chemoradiation. Mean baseline LH levels increased from 4.3 to a peak of 8.5 IU/L (p < 0.001) within 6 months after chemoradiation. Mean testosterone levels decreased from 15.4 nmol/L at baseline to 8.0 nmol/L more than 4 years after chemoradiation. Mean testosterone to mean LH ratio decreased from 4.4 at baseline to 1.1 after 48 months posttreatment, suggesting a continued decrease in Leydig cell function with time. Testicular dose was measured in 5 patients. Median dose was 4 Gy (range, 1.5-8.9 Gy). Chemoradiation in men with rectal cancer causes persistent increases in FSH and LH levels and decreases in testosterone levels.

Black cohosh has central opioid activity in postmenopausal women

To test whether black cohosh (BC) exhibits an action on the central endogenous opioid system in postmenopausal women. This was a mechanistic study conducted in the same individuals of luteinizing hormone pulsatility with a saline/naloxone challenge (n = 6) and positron emission tomography with [C]carfentanil, a selective micro-opioid receptor radioligand (n = 5), before and after 12 weeks of unblinded treatment with a popular BC daily supplement. BC treatment for 12 weeks at a standard dose (Remifemin, 40 mg/day) had no effect on spontaneous luteinizing hormone pulsatility or estrogen concentrations. With naloxone blockade, there was an unexpected suppression of mean luteinizing hormone pulse frequency (saline vs naloxone = 9.0 +/- 0.6 vs 6.0 +/- 0.7 pulses/16 h; P = 0.056), especially during sleep when the mean interpulse interval was prolonged by approximately 90 minutes (saline night interpulse interval = 103 +/- 9 min vs naloxone night interpulse interval = 191 +/- 31 min, P = 0.03). There were significant increases in mu-opioid receptor binding potential in the posterior and subgenual cingulate, temporal and orbitofrontal cortex, thalamus, and nucleus accumbens ranging from 10% to 61% across brain regions involved in emotional and cognitive function. In contrast, binding potential reductions of lesser magnitude were observed in regions known to be involved in the placebo response (anterior cingulate and anterior insular cortex). Using two different challenge paradigms for the examination of central opioid function, a neuropharmacologic action of BC treatment was demonstrated in postmenopausal women.

Oestrogen‐Dependent Stimulation of Luteinising Hormone Release by Galanin‐Like Peptide in Female Rats

Galanin-like peptide (GALP), a ligand for three types of galanin receptor, is reported to have a role in regulating luteinising hormone (LH) release in male rodents and primates, but its role in LH release in female rodents remains controversial. The present study was conducted to test whether GALP has a stimulatory role in regulating LH secretion in female rats. The effect of i.c.v. infusion of GALP (5 nmol) on pulsatile LH release was investigated in Wistar-Imamichi strain female rats, or lean and obese Zucker rats. In oestradiol-17beta (oestradiol)-primed ovariectomised (OVX) Wistar-Imamichi female rats, i.c.v. infusion of GALP caused a gradual increase in LH release for the first 1.5 h after the infusion followed by an increased LH pulse frequency during the next 1.5 h, resulting in a significant increase in the mean LH concentrations and baseline levels of LH pulses throughout the sampling period and in the frequency of LH pulses at the last half of the period compared to vehicle-treated controls. The stimulatory effect of GALP was oestrogen-dependent because the same GALP treatment did not affect LH release in OVX rats in the absence of oestradiol. In lean Zucker rats, LH pulses were found in oestradiol-primed OVX individuals and central GALP infusion increased mean LH concentrations in the last half of the period. By contrast, few LH pulses were found in oestradiol-primed OVX obese Zucker rats reportedly with lower hypothalamic GALP expression. Central GALP infusion caused an apparent but transient increase in LH release, resulting in the significant increase in all pulse parameters of LH pulses compared to vehicle-treated controls in the first half of the sampling period. These results suggest that hypothalamic GALP is likely involved in stimulating GnRH/LH release, and that the stimulatory effect of GALP on LH release is oestrogen-dependent in female rats.

Total salpingectomy during abdominal hysterectomy: Effects on ovarian reserve and ovarian stromal blood flow

To investigate the short- and medium-term consequences of performing total salpingectomy during abdominal hysterectomy (without oophorectomy) on certain ovarian reserve parameters and blood flow velocity measurements through the ovarian stroma. Twenty-four patients were recruited and randomized into two groups. Group 1 patients (n = 12) underwent total hysterectomy and complete excision of the fallopian tubes bilaterally. In group 2 (classical approach), fallopian tubes were removed partially leaving behind the neighboring paraovarian tissue. Pre- and postoperative (at 1 and 6 months) serum follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol values, ovarian volume estimation by transvaginal ultrasound, and ovarian stromal blood flow Doppler velocimetry were assessed during the early follicular phase. Mann-Whitney U-test, Student's t-test and Freidman's test were used for comparisons. Baseline data were similar across the groups (P > 0.05). Mean FSH, LH, estradiol values, and ovarian volume were unchanged after both of the techniques. However, mean pulsatility index, resistance index, and systole/diastole (S/D) ratio were significantly decreased in both groups compared to baseline values (group 1, P = 0.027, P = 0.018, and P = 0.013, respectively; group 2, P = 0.01, P = 0.002, and P = 0.0001, respectively). Postoperative decline in the mean pulsatility index was more pronounced (P = 0.02) in group 2 (partial removal). It appears that complete removal of fallopian tubes during hysterectomy has no advantageous effect on ovarian blood supply. It might be important to protect the ovarian blood supply as much as possible while performing hysterectomy in the reproductive period.

Circulating estradiol suppresses luteinizing hormone pulse frequency during dietary restriction

The influence of dietary restriction on the negative feedback potency of 17-β-estradiol (E 2) was evaluated in both castrated male (wethers) and female sheep (OVX ewes) during the breeding season. In study 1, OVX ewes received maintenance or restricted dietary energy for 7 weeks or maintenance energy for 6 weeks prior to a 5 day fast ( n = 12 ewes/feeding group). Estradiol (0.31 μg E 2/50 kg/h) or vehicle (10% EtOH-saline) was continuously infused into half the animals in each dietary treatment for the final 54 h of the study. The dynamic pattern of LH secretion was assessed during the final 6 h of infusion. Estradiol inhibited luteinizing hormone (LH) pulse amplitude independent of nutrition ( P = 0.02); fasting increased mean LH, LH peak height, and LH nadir in the absence of E 2 ( P = 0.004, P = 0.02, and P = 0.02, respectively); while E 2 inhibited pulse frequency ( P = 0.02) and increased peak width ( P = 0.04) in restricted ewes. Interestingly, despite uniform E 2 delivery, serum concentrations of E 2 differed with feeding status. Therefore, 12 wethers were infused with 0.31 μg E 2/50 kg/h (6 fed, 6 fasted) and six wethers received 0.19 μg E 2/50 kg/h (fasted) to establish similar serum concentrations of E 2 in fed (0.31 μg/50 kg/h) and fasted (0.19 μg/50 kg/h) wethers. When fed and fasted wethers had uniform serum concentrations of E 2 LH pulse frequency was suppressed ( P < 0.05) in fasted relative to fed animals, supporting the postulate that energy restriction enhances the E 2 negative feedback potency. Collectively, these studies demonstrate that nutrition affects E 2 feedback potency and clearance.

MOLECULAR SPECIES OF PROSTAGLANDINS MEDIATING STRESS-INDUCED SUPPRESSION OF GONADOTROPIN SECRETION IN THE BRAIN

It is well established that reproductive function is suppressed under stress conditions. We have previously shown that all the infectious (lipopolysaccharide), hypoglycemic (2-deoxyglucose) and restraint stress suppressed pulsatile release of luteinizing hormone (LH), which was associated with an increase in cyclooxygenase-2 expression in the brain. The suppression of LH pulses by these stressors was much more enhanced by andrenalectomy. On the other hand, both corticosterone and indomethacin similarly attenuated the suppressive effect of the stressors on LH pulses. These observations suggest that prostaglandins (PG) are involved in stress-induced suppression of LH pulses. In the present study, in order to determine which subtype of PGs is involved in suppressing LH pulses, we intracerebroventricularly administered 3 major PG subtypes, i.e. PGF2α, PGD2, and PGE2. We observed LH pulses in ovariectomized rats for 3 hours by sequential blood sampling of 5 min-intervals. PGs were injected 1 h after the start of blood sampling. First, we treated animals with each PG in 3 increasing doses (0.1, 1 and 10 μg). PGF2α did not have any influence on LH pulsatility at all the doses used. PGD2 induced a dose-dependent increase in the amplitude of LH pulses while it did not affect the frequency of LH pulses and mean LH concentrations. On the other hand, PGE2 dose-dependently induced a transient increase and subsequent decreased in both mean LH concentrations and pulse amplitude, and strongly suppressed LH pulse frequency at the highest dose. Secondly, we co-injected PGF2α (5 μg) and PGE2 (5 μg), whose syntheses are known to simultaneously increase under infectious stress conditions. This resulted in a transient suppression of LH pulses in all the 3 parameters; frequency, amplitude, and mean concentrations. These results, together with our previous findings, suggest that PGE2, independently or together with PGF2α, in the brain plays a role in suppressing LH pulses as a common mediator of stressors, and that glucocorticoids maintain reproductive function by decreasing the synthesis of these PGs. (poster)

Acceleration of Luteinizing Hormone Pulse Frequency in Adolescent Girls with a History of Central Precocious Puberty with versus without Hyperandrogenism

Some adolescents with a history of idiopathic central precocious puberty (ICPP) develop hyperandrogenism. Hypothesis: Luteinizing hormone (LH) hypersecretion could be a common mechanism underlying ICPP and polycystic ovary syndrome. Aim: To explore the GnRH-LH axis in those patients. Design: To compare overnight LH secretion in 7 healthy adolescents (CG) with that in patients with prior ICPP [5 with (CPPA) and 7 without (CPPB) hyperandrogenism]. To analyze daytime LH secretion in those patients. Methods: LH secretion was quantified by immunofluorometry and deconvolution analysis. Results: Nighttime mean LH (international units/liter) was higher in CPPA (6.9 ± 1.5) than in CPPB (3.2 ± 0.4, p < 0.05) and CG (2.9 ± 0.4, p < 0.01). Deconvolution analysis revealed a greater nighttime LH frequency (pulses/hour) both in CPPA (0.91 ± 0.06, p < 0.01) and CPPB (0.74 ± 0.02, p < 0.05) than in CG (0.45 ± 0.07). CPPA patients maintained a higher frequency than CPPB. Pulsatile LH production was greater in CPPA than in CG (50 ± 12 vs. 18 ± 3 IU/l/day, p < 0.01). Daytime mass of LH released per burst and pulsatile production rate were significantly greater in CPPA than in CPPB patients. Conclusions: Hyperandrogenic adolescents with prior ICPP show increased pulsatile LH secretion. Augmentation of LH pulsatility may predispose to or cause hyperandrogenism in some adolescents with a history of precocious puberty.

Characteristics of the urinary luteinizing hormone surge in young ovulatory women

To define characteristics of the luteinizing hormone (LH) surge in urine. Observational study. Academic center. 46 women aged 20 to 35 years with regular menstrual cycles. Collected first morning urine daily, throughout one menstrual cycle. Urinary LH, follicle-stimulating hormone (FSH), estrone conjugate (E1C), and pregnanediol-3-glucuronide (PDG). Three women lacked LH surges. Mean LH surge: start = day 14.5 (+/-3.6 SD) (range: 9-26); peak = 41.2 mIU/mg creatinine (+/-20 SD) (range: 12.1-104.0); fold increase = 7.7 (+/-3.0 SD) (range: 2.5-14.8); duration = 7.6 days (+/-1.5 SD) (range: 5-11). The onset of LH surge was of two types: rapid onset (within 1 day) (42.9%) or gradual onset (2 to 6 days) (57.1%). Configurations of LH surges were of three types: spike (41.9%), biphasic (44.2%), or plateau (13.9%). All LH surges demonstrated a gradual decrease to baseline. Three women (7%) did not have FSH rises coincident with LH surges. All displayed E1C rises during the middle to late follicular phase. The LH surges that result in ovulation are extremely variable in configuration, amplitude, and duration. The FSH rise does not seem essential for ovulation. However, an E1C rise occurred in all cycles, confirming the critical role of estrogen in induction of the LH surge.

Study of Enteral versus Parenteral Application of the Gonadotropin Releasing Hormone Agonist Gonadorelin[6-D-Phe] (D-Phe6-LHRH) on LH Secretion in Goettinger Miniature Pigs

With respect to the assessment of residue situation and as a part of preclinical trials to determine the biological activities of potential gonadotropin releasing hormone (GnRH) residues in porcine organisms the GnRH agonist Gonadorelin[6-D-Phe] (D-Phe(6)-LHRH) was administered either enterally or intramuscularly (i.m.) to female Goettinger miniature pigs in order to evaluate the GnRH-induced luteinizing hormone (LH) surge. Gilts received an (i) enteral application of 10 mg D-Phe(6)-LHRH via a probang (enteral group, n=7), (ii) i.m. injection of 0.1 mg D-Phe(6)-LHRH (parenteral group, n=5), or (iii) saline injection (control group, n=4). The GnRH and saline applications were repeated every second day with up to seven repetitions. Blood samples were collected via previously fitted jugular catheters immediately before injections, over an 8 h period in 1 h intervals beginning 2 h after injections, and at 24, 26, 28 and 30 h after applications. Enteral application of D-Phe(6)-LHRH induced an LH surge in 23 of 30 treatments. All gilts in the parenteral group exhibited LH release after each D-Phe(6)-LHRH application (P<0.05), whereas no LH surges were observed after saline injection in the control group. A significant (P<0.05) LH rise to mean maximum LH concentrations of 3.25 +/- 0.43 and 3.05 +/- 0.26 ng/ml occurred in both the enteral and parenteral groups, but there was no difference in the time interval after GnRH (2.6 +/- 0.3 vs. 2.3 +/- 0.3 h) and the mean duration of LH peak (6.5 +/- 0.4 and 6.8 +/- 0.3 h) between the treatment groups. In conclusion, (i) enteral application of 10 mg D-Phe(6)-LHRH induced LH release in a physiological range from the pituitary of female minipigs, and (ii) neither an accumulative effect nor a cumulative LH response were found after repeated GnRH application. Furthermore, (iii) in regard to consumer protection and gonadotropin secretion, D-Phe(6)-LHRH residues can be excluded from having long-term effects.

Hyperprolactinemia And Hypergonadotropins In Infertile Males With Sever Oligospermia And Azoospermia

Serum prolactin (PRL), luteinizing hormone (LH), and follicle stimulating hormone (FSH) were analyzed in 120 infertile male including: 78(65%) asthenozoospermic, 24(20%) sever oligospermic, 10(8.3%), oligospermic, and 8(6.7%) azoospermic using immunometric assay. Hormonal seric values were correlated with sperm count, motility, and antisperm antibody as detected by Latex Agglutination Test . No clinical importance of autoantibody was appeared in all groups of subjects investigated. A significant week correlation was found between serum LH and sperm count in all infertile males (p=0.002) but not motility, whereas PRL and FSH showed an inverse relationship with motility (r = -0.469 p<0.005, r = -0.316 p< 0.005) respectively. The mean PRL level (reference range 2.5-17 ng/ml) was found to be higher in sever oligospermia and azoospermia (mean 17.9 ±12.7 and 18.6 ±11.7 respectively). On the other hand, the mean LH levels (reference range 0.8-7.6 mIU/ml) and FSH (reference range 0.7-11.1 mIU/ml) was found to be higher in azoospermia (19.9±14.9 and 24.8±32.4 respectively). Increasing profile of FSH and PRL is useful in routine investigation of azoospermic male (p=0.001). These data demonstrate that when using lower semen parameters, the most common serum hormone abnormality is increased in PRL and gonadotrophins. The study gives an impression concerning serum PRL, FSH, and LH in infertile males in Jordan.

Photoperiod and luteinizing hormone secretion in domestic and wild pigs

During seasonal anoestrus (long-days), oestradiol can effectively inhibit the pulsatile secretion of luteinizing hormone (LH) in sheep. The aim of our trial was to determine whether the same regulatory mechanism exists in the pig. Altogether, 20 ovariectomized and oestradiol-implanted gilts (16 domestic pigs, 4 European wild boars) were randomly allocated to two treatment groups. The first group was kept under a short-day light–dark cycle of 8L:16D, and the second group under a long-day light regime of 16L:8D. After a 6-week treatment period, blood samples were taken at 20-min intervals for 12 h. After sampling, the light regimens were switched. Sampling was then repeated following another 6 weeks of treatment. In both treatment groups, 2.3 LH pulses occurred every 12 h. The basal LH level was 0.7 ± 0.4 ng/ml for the short-day group and 1.0 ± 0.5 ng/ml for the long-day group. The mean LH level was 0.9 ± 0.4 and 1.3 ± 0.6 ng/ml and the LH pulse amplitude 0.5 ± 0.4 and 0.6 ± 0.5 ng/ml, respectively. The basal and mean LH levels were therefore lower in short-day gilts ( P < 0.05), while LH pulse amplitude and frequency remained unaffected by treatment. In conclusion, the 6-week period under two different light regimes resulted in higher basal LH concentration in long-day gilts but was not able to produce changes in LH frequency in prepubertal gilts.

Effects of p-Nonylphenol and 4-tert-Octylphenol on the Anterior Pituitary Functions in Adult Ovariectomized Rats

p-Nonylphenol (NP) and 4-tert-octylphenol (OP) are known to mimic the action of estrogens as endocrine disruptors. However, their acute effects on the pituitary and the hypothalamus functions in vivo have been uncertain. We therefore determined their effects on the anterior pituitary, in particular, gonadotropin secretion. Two weeks after ovariectomy, the rats were given a subcutaneous injection of 10 mg NP, 10 mg OP, 10 mg bisphenol A, 1 µg 17β-estradiol, or sesame oil alone as control. Twenty-four hours after the treatment, the expression of progesterone receptor mRNA in the anterior pituitary and the level of luteinizing hormone (LH), follicle-stimulating hormone, and prolactin were determined. The expression of progesterone receptor mRNA in the anterior pituitary was significantly increased by either NP, OP, bisphenol A, or estradiol, but bisphenol A was less effective. The level of LH was significantly decreased by either NP or OP, but not by bisphenol A and estradiol. Only estradiol significantly increased the level of prolactin. The level of follicle-stimulating hormone was unchanged by any of the treatments. To check the effects of NP and OP on pulsatile LH secretion, blood samplings were done at 6-min intervals for 3 h. Twenty-four hours after treatment in ovariectomized adult rats, we found that the injection of NP significantly decreased the amplitude of LH pulses and the mean LH concentrations, but not the frequency of LH pulses. The injection of OP significantly decreased the mean LH concentrations without affecting the frequency and amplitude of the LH pulses. Finally, the rats given an injection of NP or sesame oil were intravenously injected with 50 ng of gonadotropin-releasing hormone (GnRH) to check whether NP affected the LH secretory responsiveness of the anterior pituitary to GnRH. We found that the responsiveness to GnRH in NP-injected rats was significantly attenuated compared to the sesame oil-injected rats. The present study suggests that NP, even with a single injection, suppresses the pulsatile LH secretion in adult ovariectomized rats, probably by affecting the anterior pituitary level.

Development of quantitative real-time PCR assays for fathead minnow ( Pimephales promelas) gonadotropin β subunit mRNAs to support endocrine disruptor research

Fathead minnows ( Pimephales promelas) are a widely-used small fish model for regulatory ecotoxicology testing and research related to endocrine disrupting chemicals (EDCs). Quantitative real-time PCR assays for measuring fathead minnow gonadotropin (GtH) β subunit transcripts were developed and “baseline” transcript levels in pituitary tissue were examined over a range of age classes and spawning states. Among females, GtHβ transcripts did not vary significantly with gonadal–somatic index or gonad stage. However, in males, follicle-stimulating hormone β subunit transcripts decreased significantly with increasing gonad stage, while mean luteinizing hormone β subunit expression trended in the opposite direction. GtHβ transcript levels measured in pituitaries from fish that had spawned within the preceding 24 h were not significantly different from those from fish that were 2–3 days post-spawn. Exposure to the fungicide ketoconazole, a known steroidogenesis inhibitor, for 21 days significantly affected the abundance of GtHβ transcripts in pituitary tissue in males, but not females. This study provides critical data needed to design and interpret effective experiments for studying direct and indirect effects of EDCs on GtH subunit mRNA expression. Results of such experiments should facilitate a greater understanding of integrated system-wide responses of the fathead minnow brain–pituitary–gonadal axis to stressors including EDCs.

Assessment of Insulin Resistance in the Idiopathic Hirsutism

Background: Idiopathic hirsutism (IH) is the second most common cause of hirsutism, after polycystic ovary syndrome and occurs in about 15% of hirsute women. There are not many studies showing whether patients with IH also have insulin resistance. In the present study, we aimed to investigate the insulin sensivity in IH with non-obese and changing hormone levels during the hyperinsulinemic-euglycemic clamp. Methods: Twenty (20) non-obese women with IH (Group I) ranging in age from 20 to 30 (mean 25 ± 5) years were studied. Hirsutism in women with normal testosterone (T) levels and regular menstrual cycles is as defined IH. Twenty (20) healthy women (mean age 23 ± 2 years) (Group II) were included in this study as the control group. Insulin sensitivity was assessed with modified euglycemic insulin clamp technique. Samples of prolactin, luteinizing hormone (LH), follicle-stimulating hormone, adrenocorticotropic hormone (ACTH), dehydroepiandrosterone sulfate, cortisol, estradiol, progesterone, 17-OH progesterone (17-OHP), total T, and free T (FT) were obtained at baseline and at 2nd hour during clamp. Results: Steady-state (120 min) glucose disposal rates were higher in Group II than Group I (7.51 ± 0.83 vs. 5.76 ± 1.89 mg/kg/min). Mean FT, ACTH, cortisol, LH, prolactin and 17-OHP levels were found to have decreased statistically significantly (p < 0.05) in Group I. Mean FT, ACTH, and prolactin levels were found to have decreased statistically significantly (p < 0.05) in Group II during the clamp. Mean baseline levels of FT, LH and prolactin were greater in women with hirsutism than in the control subjects (p < 0.05). Insulin mediated glucose disposal was lower in the normal weight women with IH than in those without hirsutism. Conclusions: Mean FT, 17-OHP and dehydroepiandrosterone sulfate levels decreased during euglcemic-hyperinsulinemic clamp in IH.

Absence of Apparent Circadian Rhythms of Gonadotropins and Free α-Subunit in Postmenopausal Women: Evidence for Distinct Regulation Relative to Other Hormonal Rhythms

Aging is associated with a decrease in gonadotropin levels in postmenopausal women (PMW) and is also associated with alterations in a number of circadian rhythms. The goals of this study were to determine the presence of circadian rhythms of gonadotropins and glycoprotein free alpha-subunit (FAS) in young and old PMW. Healthy, euthyroid PMW, ages 45 to 55 years (n = 11) and 70 to 80 years (n = 11), were admitted in the morning to start a 24-h constant routine of light, temperature, position, and activity. Subjects remained awake and semirecumbent for the duration of the study and were fed hourly snacks, and activity was monitored continuously. Blood was sampled every 5 min for two 8-h periods corresponding to the estimated acrophase and nadir of the temperature rhythm. Luteinizing hormone (LH) and FAS were measured in all samples and follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), and cortisol in 20-min serum pools. Mean LH (p < 0.001), FSH (p < 0.002), and FAS (p < 0.002) were lower in older compared with younger PMW. Day/night differences in cortisol and TSH (p < 0.001) were present in all subjects. However, there were no day/night differences in LH in younger or older PMW or in FSH in younger or older PMW. There were no day/night differences in mean FAS in younger or older PMW or in FAS pulse frequency or amplitude. Thus, in controlled studies in which differences in cortisol and TSH were demonstrated, there were no day/night differences in LH, FSH, or FAS in PMW. These studies suggest that despite evidence of intact circadian rhythms of cortisol and TSH, gonadotropin secretion does not appear to follow a circadian pattern in PMW. Thus, the age-related decline in gonadotropin secretion in PMW is not associated with a dampening of circadian rhythmicity. The absence of day/night differences in FAS suggests that GnRH plays a more prominent role in FAS regulation than does thyrotropin-releasing hormone in PMW.

A 12-Month Clinical Study of LA-2585 (45.0 MG): A New 6-Month Subcutaneous Delivery System for Leuprolide Acetate for the Treatment of Prostate Cancer

The safety, efficacy and pharmacokinetics of LA-2585, a new 6-month subcutaneous depot of leuprolide acetate (Atrix Laboratories, Fort Collins, Colorado) were investigated in patients with prostate cancer. In this 12-month, open label, multicenter study 111 patients with adenocarcinoma of the prostate were administered 45.0 mg LA-2585 subcutaneously once every 6 months. The primary efficacy parameter was serum testosterone 50 ng/dl or less. Leuprolide acetate pharmacokinetics were analyzed in a subset of 28 patients. Of the 111 enrolled patients 103 (93%) completed the 12-month study. Eight patients withdrew due to nonmedical reasons in 1, disease progression in 5 and cardiovascular disease in 2. By day 28, 108 of the 109 remaining patients (99%) achieved testosterone suppression, while 1 who never attained suppression was withdrawn at day 85. Mean time to castrate suppression was 21.2 days (median 21). At study completion 102 of 103 patients (99%) were below medical castrate testosterone levels of 50 ng/dl (mean +/- SE 12.3 +/- 2.1 ng/dl) with 91 of 103 (88%) at less than 20 ng/dl. Mean luteinizing hormone decreased from 6.98 +/- 0.48 mIU/ml at baseline to 0.23 +/- 0.14 mIU/ml at month 12. Luteinizing hormone was consistently below 1 mIU/ml. Mean prostate specific antigen decreased 97% from 39.8 +/- 21.5 ng/ml at baseline to 1.2 +/- 0.3 ng/ml at 12 months. No clinically significant flare reactions were observed. The most common treatment related adverse event was mild to moderate hot flashes. LA-2585 (45.0 mg depot) consistently produced and maintained safe and effective serum testosterone suppression with total serum testosterone well below the medical castrate level of less than 50 ng/dl.

Role of Noradrenergic Receptors in the Bed Nucleus of the Stria Terminalis in Regulating Pulsatile Luteinizing Hormone Secretion in Female Rats

The bed nucleus of the stria terminalis (BNST) is one of the brain areas densely innervated by noradrenergic neurons originating in the brain stem. The present study aims to determine the role of noradrenergic receptors in the BNST in regulating pulsatile luteinizing hormone (LH) secretion in female rats. Ovariectomized (OVX) or estrogen-primed OVX (OVX+E2) rats received three 1-h-interval injections of 0.05 micromol of noradrenaline (NA), phenylephrine (alpha1-adrenergic receptor agonist), clonidine (alpha2-agonist), or isoproterenol (beta-agonist) into the BNST. Injection of NA or alpha1-adrenergic agonist into the BNST strongly suppressed pulsatile LH secretion in OVX+E2 rats with a significant (P < 0.05) decrease in the mean LH level for 3 h and LH pulse frequency, but alpha2-and beta-agonists did not affect any of the LH pulse parameters. In OVX animals, alpha1- and alpha2-adrenergic agonists caused a significant change in LH pulse frequency and amplitude, respectively, though the effect was not as apparent as the NA- or alpha1-agonist-induced changes in OVX+E2 animals. These results indicate that NA inputs to the BNST suppress pulsatile LH secretion via alpha1-adrenergic receptors and that estrogen enhances this suppression.

Twenty-four-hour secretion patterns of luteinizing hormone in mithuns ( Bos frontalis)

A 24 h secretion pattern of luteinizing hormone (LH) was not available in mithun ( Bos frontalis), a semi-wild ruminant. To characterize the 24 h LH profiles, six female mithun calves (age 7.8 ± 0.5 months and 102.5 ± 5.6 kg; group I) and six female mithuns averaging 25.4 months of age and 240 kg (group II) were selected from the National Research Centre on Mithun farm and were maintained in semi-intensive systems. Blood samples collected from all the animals at 30 min intervals for 24 h were assayed for plasma LH. Plasma progesterone was also estimated in twice-a-week samples collected for 6-week period preceding each 24 h sampling to assess whether any animal had begun ovarian cyclicity. The body weights of all animals were also recorded weekly during the 6-week period. LH patterns consisted of frequent pulses of varying amplitude. Luteinizing hormone pulses occurred at an average frequency of 0.28/h (≈7 pulses/24 h) and 0.15/h (≈3.5 pulses/24 h) for mithuns of groups II and I, respectively, the rate did not differ markedly among mithuns within each group but was significantly different between the groups. Similarly, the magnitude of LH secretory pulses did not vary among mithuns within the group but was significantly higher in group II than in group I animals. In group II, the LH peaks averaged 1.59 and 1.00 ng/ml in mithun having the highest and lowest LH peaks, respectively and the corresponding values for group I mithuns were 0.66 and 0.51 ng/ml. Mithun with higher peak LH levels also had higher mean LH concentrations ( P < 0.05). The mithuns of group II had significantly higher plasma progesterone concentration (0.89 ± 0.02 ng/ml) than those recorded in group I mithuns (0.26 ± 0.01 ng/ml). Plasma progesterone profiles suggested that no animal reached puberty. In conclusion, there was higher LH secretion with higher pulsatility and greater amplitude in group II mithuns than exhibited in mithuns of group I and the prepubertal mithuns of group II were in approaching puberty, which were also indicated by their plasma progesterone profiles, critical body weight and age required to attain puberty, in addition to higher pulsatility of LH secretion.