Increase In Serum LH Concentrations Research Articles

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

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

LH regulated gene expression in the ovary of PCOS women, a role for PEG3 and TCF21

Polycystic ovary syndrome (PCOS) is the most common cause of anovulation and affect 5-10% of women in the reproductive age. Compared to normal cycling women, those with PCOS generally exhibit increased serum LH concentrations, low-normal FSH levels. Several observations suggest that excessive LH stimulation plays an important role in the pathophysiology of PCOS. In this study LH regulated gene expression was studied in ovaries of PCOS women.

Novel role of the anorexigenic peptide neuromedin U in the control of LH secretion and its regulation by gonadal hormones and photoperiod

Neuromedin U (NMU) is a widely spread neuropeptide, with predominant expression at the gastrointestinal tract and brain, putatively involved in the regulation of a diversity of biological functions, including food intake, energy balance and circadian rhythms; all closely related to reproduction. Yet, the implication of NMU in the control of the gonadotropic axis remains scarcely studied. We report herein analyses on the hypothalamic expression and function of NMU in different physiological and experimental states of the rat reproductive system. Expression of NMU mRNA at the hypothalamus was persistently detected along female postnatal development, with maximum levels in adulthood that fluctuated across the cycle and were modulated by ovarian steroids. Acute central administration of NMU evoked increases of serum LH levels in pubertal female rats, while repeated injection of NMU tended to advance vaginal opening. Likewise, central injection of NMU increased serum LH concentrations in cycling female rats, with peak responses in estrus. In contrast, NMU significantly inhibited preelevated LH secretion in gonadectomized and kisspeptin-treated rats. Finally, in noncycling females due to photoperiodic manipulation (constant light), hypothalamic NMU mRNA levels were markedly depressed, but relative LH responses to exogenous NMU were significantly augmented. All together, our present data support a predominant stimulatory role of NMU in the control of the female gonadotropic axis, which appears under the influence of developmental, hormonal, and photoperiodic cues, and might contribute to the joint regulation of energy balance, biological rhythms, and reproduction.

A pharmacokinetic and endocrine comparison of recombinant follicle-stimulating hormone and human menopausal gonadotrophin in polycystic ovary syndrome

Elevated LH concentrations are frequently encountered in patients with polycystic ovary syndrome (PCOS) and increased LH (either endogenous or superimposed through the use of HMG) may have detrimental effects on reproductive function. In spite of this, FSH-only products and HMG have been used indiscriminately for ovulation induction – on the basis that the administration of HMG to patients with PCOS, who are not receiving GnRH agonists, does not result in significant increases in serum LH concentrations as judged by daily single blood samples. However, both endogenous and exogenous LH have a relatively short terminal half-life and studies have reported normal serum LH, but abnormal urinary LH and emphasized that early morning urinary measurements are more informative than those in serum because they reflect nocturnal LH secretion. Therefore, the present study was undertaken to perform a pharmacokinetic and endocrine comparison of recombinant human FSH and HMG in PCOS patients including LH measurements in the urine. Five PCOS patients receiving s.c. recombinant human FSH (rhFSH) and five PCOS patients receiving i.m. HMG for ovulation induction according to a chronic low-dose step-up regimen underwent blood and urine sampling at the following study points: Point 0 was the day of HCG injection; Points 1 to 5 corresponded to days HCG −1 to −2; −3 to −4; −5 to −6; −7 to −8; and −9 to −10; respectively. Serum hormone measurements included oestradiol, FSH, LH, progesterone, inhibin A, androstenedione, testosterone, and free testosterone index. FSH and LH were also measured daily in 8-h urine samples reflecting overnight renal urine secretion. Hormone concentrations calculated as the area under the curve showed that both FSH and LH concentrations in urine were significantly higher in HMG group than in group rhFSH. It is concluded that both LH and FSH concentrations significantly accumulate in the urine of PCOS patients receiving HMG for ovulation induction in a chronic low-dose protocol as compared with rhFSH treatment.

Role of Na+ and Ca2+ channels in the preoptic LH surge generating mechanism in proestrous rats.

We studied whether Na+ and Ca2+ channels are involved in the neural mechanism responsible for the surge of gonadotropin-releasing hormone (GnRH) in proestrous rats. In experiment 1, female rats in proestrus were i.p. injected at 1345 h with pentobarbital sodium (35 mg/kg) to block spontaneous surge of LH and electrical stimulation was applied between 1400 and 1600 h to the preoptic area (POA) together with POA injection of 0.5 microl saline containing the Na+ channel blocker tetrodotoxin (TTX) at a concentration of 1 microM, 2 microM, or 5 microM. Since 5 microM TTX completely blocked the increase in serum LH concentrations evoked by the POA stimulation, we used this concentration in experiment 2 to observe the TTX effect on the spontaneous LH surge. In experiment 2, bilateral injections of 1.5 microl of 5 microM TTX at 1430 h in the POA in proestrous rats postponed the peak time and reduced the peak level of the LH surge. In experiment 3, bilateral injections of 1.5 microl of 5 microM L-type Ca2+ channel blocker nifedipine at 1430 h in the POA completely blocked the LH surge. Since the cell bodies of GnRH neurons are primarily concentrated in the POA in rats, these results suggest that both voltage-sensitive Na+ channels and Ca2+ channels contribute to the generation of action potentials at GnRH cell bodies for the surge release of GnRH.

Gonadotropin secretory dynamics in polycystic ovary syndrome

Whereas alterations in gonadotropin secretion have long been recognized in women with the polycystic ovary syndrome (PCOS), neither the mechanisms subserving these abnormalities nor the full ramifications of such altered secretion are completely understood. Within the past year several studies have examined fundamental aspects of gonadotropin secretion in PCOS, and the relation of such secretion to other hormonal systems. Increased serum LH concentrations in women with PCOS have again been shown to reflect both an increase in the number and amplitude of individual LH pulses and enhanced LH interpulse (basal) secretion. Perhaps paradoxically, short-term fasting in women with PCOS results in increased rather than decreased LH secretion. Whereas there is a strong positive relation between LH and inhibin B in women with PCOS, obesity negatively correlates with inhibin B in both normal and women with PCOS. Thus, the concentration of serum inhibin B in women with PCOS represents a balance between the positive and negative effects of LH and obesity, respectively. The LH secretory process itself in women with PCOS is disorderly, presumably reflecting abnormal regulation. Secretion of target hormones (eg, androstenedione) is also less orderly in women with PCOS. Moreover, the coupling of several hormone systems including LH–testosterone, LH–androstenedione and LH–leptin is disturbed in women with PCOS. The latter is consistent with the premise that both the feedforward (eg, LH stimulating testosterone secretion) and the feedback (eg, testosterone modulating the GnRH-LH secretory system) are deranged in PCOS.

Targeted cytotoxic analogue of luteinizing hormone-releasing hormone (LH-RH) only transiently decreases the gene expression of pituitary receptors for LH-RH.

A cytotoxic analogue of LH-RH, AN-207, consisting of 2-pyrrolinodoxorubicin (AN-201) linked to carrier [D-Lys6]LH-RH, was developed for targeted therapy of cancers expressing LH-RH-receptors. To determine its possible side-effects on the pituitary gland, we investigated the gene expression of pituitary LH-RH-receptors and LH secretion in ovariectomized female and normal male rats after treatment with the maximum tolerated dose of AN-207. The effect of AN-207 on the gene expression of the pituitary GH-RH-receptors and GH secretion was also assessed in male rats. Five hours after a single i.v. injection of AN-207 at 175 nmol/kg, there was a 39-51% decrease in mRNA expression for the pituitary LH-RH-receptors in male and female rats. The carrier, at an equimolar dose, caused a similar reduction (37-39%), whereas the cytotoxic radical AN-201, at an equitoxic dose (110 nmol/kg), produced only a 12-24% decrease (NS) in the mRNA expression of LH-RH-receptors. AN-207 and the carrier analogue induced a comparable 90-100-fold increase in serum LH concentrations in male rats, and the same 12-fold elevation in OVX rats at 5 h. Seven days after treatment with AN-207, the mRNA levels for the LH-RH receptors and the serum LH concentration were back to normal in both sexes. AN-207, the carrier, and AN-201 had no significant effect on the expression of mRNA for GH-RH-receptors in the pituitary. In vitro, a continuous perfusion of pituitary cells with 10 nM AN-207 did not affect the hormone-releasing function of the targeted LH cells or the nontargeted GH cells. Our results demonstrate that cytotoxic LH-RH analogue AN-207, at the maximum tolerated dose causes only a transient decrease in the gene expression of the pituitary LH-RH receptors, and the levels of mRNA for LH-RH receptor fully recover within 7 days. Moreover, the carrier hormone moiety, and not the cytotoxic radical in AN-207 is responsible for this transient suppression. Our findings suggest that the therapy with cytotoxic LH-RH analogues will not inflict permanent damage to pituitary function.

Fos expression in gonadotropin-releasing hormone neurons by naloxone or bicuculline in intact male rats

Double immunocytochemistry for Fos and GnRH was performed after the intravenous infusion of naloxone or bicuculline. Either naloxone or bicuculline significantly increased serum LH concentrations. After the naloxone infusion, some Fos-positive GnRH neurons were found from the preoptic area to the basal hypothalamic area, whereas those were found from the diagonal band of Broca to the preoptic area after the bicuculline infusion. These results suggest the distribution of GnRH neurons activated by naloxone and bicuculline in intact male rats.

On the mechanism of the positive feedback action of estradiol on luteinizing hormone secretion in the rhesus monkey.

In women and rhesus monkeys, both the negative and positive feedback actions of estradiol (E2) on gonadotropin secretion (inhibition followed by a surge) can be exerted directly at the level of the pituitary gland. We have tested the hypothesis that the positive feedback action of E2 represents but an "escape" from its negative feedback inhibition of gonadotropin secretion consequent to a desensitization of the gonadotropes occasioned by sustained exposure to elevated concentrations of the steroid. We have attempted to replicate such a desensitization by blocking the negative feedback action of E2 by the administration of a potent estrogen receptor antagonist devoid of any agonistic properties (ZM 182,780) to rhesus monkeys in the midfollicular phase of the menstrual cycle (n = 14). The estrogen antagonist, administered at a dose that in separate experiments completely blocked both the negative and the positive feedback effect of exogenous E2 on pituitary LH secretion, failed to produce a surge-like increase in serum LH concentrations. The present results do not support the hypothesis that the LH surge is the consequence of the removal of the negative feedback action of E2. Evidence is presented that ZM 182,780, in contrast to its inhibition of E2-induced LH surges, cannot block the inhibition of hypothalamic GnRH pulse generator activity by E2.

Facilitation or inhibition of the estradiol-induced gonadotropin surge in the immature rat by progesterone: regulation of GnRH and LH messenger RNAs and activation of GnRH neurons.

We have developed and extensively characterized immature female rat models to demonstrate inhibition or facilitation of the estradiol (E2)-induced gonadotropin surge by progesterone (P). We show here that the surge of free alpha-subunit is regulated similarly by P in these models. To investigate the possibility that P alters the biosynthesis of GnRH and/or LH, we measured levels of LH subunit mRNAs by Northern blot hybridization and GnRH mRNA by a solution hybridization-RNase protection assay. In the P inhibition model, alpha-subunit mRNA was significantly decreased when P was administered together with E2 for 32 or 48 h, and LHbeta, at 29 h. In the facilitation model, neither alpha-subunit nor LHbeta mRNA increased with premature and enhanced release of LH and free alpha-subunit. Levels of GnRH mRNA in E2-treated rats were significantly higher on the afternoon of the LH surge than on that or the following morning. There was no effect of P on GnRH mRNA levels, however, before, during, or after the LH surge in either paradigm. The time course of activation of GnRH neurons in P-facilitated rats was determined by double-label immunocytochemistry for GnRH and cFos. When serum LH concentrations were basal there was no expression of cFos in GnRH neurons. LH secretion in P-facilitated rats was initiated at 14.00 h and remained elevated until at least 19.00 h. During this time 63-78% of GnRH neurons were cFos positive. Both serum LH concentrations and the percentage of cFos-activated GnRH neurons were significantly lower in control rats treated with E2 alone than in those treated also with P. 1) suppression of LH and free alpha-subunit secretion by P can be accounted for at least partly by suppression of alpha-subunit mRNA levels; 2) P facilitation is not associated with changes in LH subunit or GnRH mRNA levels; 3) the large proportion of cFos-positive GnRH neurons in P-facilitated rats closely parallels increases in serum LH concentrations but is not accompanied by changes in GnRH mRNA levels. It is likely, therefore, that P acts in the facilitation model to trigger release of pre-existing GnRH stores by altering synthesis or activity of neuro-transmitters/neuropeptides involved in GnRH regulation and/or release of LH stores by altering, for example, pituitary responsiveness to GnRH (including self-priming) and components of the LH secretory apparatus. Similar possibilities may also obtain for the blockade of the gonadotropin surge in the inhibition model.

Interstitial orchitis with impaired steroidogenesis and spermatogenesis in the testes of rabbits infected with an attenuated strain of myxoma virus.

The pathogenesis of infertility associated with acute viral orchitis was investigated in a rabbit model. Infection of postpubertal male European rabbits with an attenuated strain of myxoma virus caused systemic disease with viral replication to high titres in the testes. Infected rabbits developed an interstitial orchitis and epididymitis. This was associated with degeneration of the seminiferous epithelium, decreased serum testosterone concentrations and increased serum LH concentrations. Virus was localized within the interstitial cells. Clearance of infectious virus from the testis occurred between day 20 and day 30 after infection, although viral DNA could still be detected by polymerase chain reaction at 120 days. Viral clearance was associated with a return to normal serum testosterone and LH concentrations. Anti-sperm antibodies were present in the serum as early as 5 days after infection and declined during the recovery phase. Rabbits were infertile at 60 days but returned to normal fertility 60-90 days after infection.

Fos expression by naloxone in LHRH neurons of the mediobasal hypothalamus and effects of pentobarbital sodium in the proestrous rat.

Because Fos is thought to be induced in neurons that are activated, we examined whether luteinizing hormone-releasing hormone (LHRH) neurons expressed Fos protein when they were stimulated by an opioid receptor antagonist naloxone (NAL), expecting to identify LHRH neurons which are regulated by opioid neurons directly or indirectly. Further, we examined whether an ovulation-blocking dosage of pentobarbital sodium (PB) would affect the NAL-induced Fos expression. Female rats were infused with naloxone (5 mg/kg/h) for 90 min (10.00-11.30) in the morning of proestrus, during which infusion blood sampling was done, and were killed by i.v. injection with an overdose of PB at 11.30-12.00. Dual immunoperoxidase/immunofluorescence staining for both Fos and LHRH revealed that some LHRH immunoreactive (ir) neurons in the forebrain expressed Fos-ir, associated with an increase in serum LH concentrations, but little co-localization was found in rats in proestrus which were infused with saline as the control. The proportion of LHRH-ir neurons which expressed Fos-ir was about 35-62% in the caudal part of the forebrain including the mediobasal hypothalamus, and this was larger than that (10%) in the rostral part of the forebrain including the preoptic area. PB injection (32 mg/kg bw, i.p.) 15 min prior to the beginning of NAL infusion significantly enhanced the increase in LH secretion due to NAL, and also enhanced Fos-ir expression in LHRH-ir neurons. Together with the well-established fact that PB blocks the LHRH surge generator and our previous findings that NAL stimulates the LHRH pulse generator even in the PB-blocked proestrous rat, these results strongly suggest that the LHRH pulse generator exists in the mediobasal hypothalamus which contains LHRH neurons that are responsive to NAL and express Fos protein.

Castration-induced decrease in the activity of medial preoptic and tuberoinfundibular GABAergic neurons is prevented by testosterone.

We recently determined that castration specifically decreased GABA turnover in discrete rostral and mediobasal hypothalamic structures. This study aimed to investigate whether testosterone could stimulate GABAergic neuronal activity in these hypothalamic GABAergic neurons in the castrate rat, and to compare the effects of episodic testosterone replacement with the constant levels provided by subcutaneous testosterone implants. Animals were divided into 4 experimental groups: intact, 48 h castrate, 48 h castrate+testosterone capsules (2 x 30 mm Silastic implants, 1.57 mm ID, 3.18 mm OD) and 48 h castrate+testosterone injections (100 micrograms/injection s.c., every 8 h). GABA concentrations were measured in 4 microdissected brain regions either before or 60 min after inhibition of the GABA degrading enzyme, GABA transaminase, by injection of aminooxyacetic acid (AOAA, 100 mg/kg i.p.). The rate of GABA accumulation in the tissue following injection of AOAA was used as an index of GABAergic neuronal activity. Castration resulted in a 10-fold increase in serum LH concentrations compared with intact rats. Either mode of testosterone administration completely prevented this castration-induced LH rise. In the diagonal band of Broca at the level of the organum vasculosum of the lamina terminalis, the medial preoptic nucleus and in the median eminence, GABA turnover was significantly reduced by castration to approximately 50% that of intact rats. Either testosterone implants or testosterone injections prevented this castration-induced decrease in GABA turnover, such that the turnover rates were not significantly different from intact rats. There was no effect of castration with or without testosterone replacement in the cingulate cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of opioid blockade and GnRH administration upon luteinizing hormone secretion in patients with anorexia nervosa during the stages of weight loss and weight recovery.

We examined the functional status of the hypothalamic-opioid system involved in LH secretion and the pituitary LH sensitivity and reserve in patients with anorexia nervosa were studied during body weight loss and weight recovery. We measured the temporal relationship between weight recovery, expression of hypothalamic-opioid activity and pituitary GnRH responsiveness, and resumption of ovulatory cycles. Five patients with anorexia nervosa were prospectively studied during weight loss and amenorrhoea, subsequently when they reached their ideal body weight but still remained amenorrhoeic and thereafter every 6 months until resumption of ovulatory cycles; one patient was studied only during weight loss, two during ideal body weight and amenorrhoea and one during ideal body weight and ovulatory cycles. Blood was sampled every 10 minutes over a 16-hour period on two alternate days. On study day 1 (control day), patients received two sets of saline infusion every 6 hours and one saline bolus at the beginning of the seventh hour; on study day 3 (experimental day), they received a saline infusion during the first 6 hours, an intravenous bolus of naloxone (20 mg) at the beginning of the seventh hour and then a continuous naloxone infusion (1.6 mg per hour) during the ensuing 6 hours. Pituitary LH sensitivity and reserve were assessed on both study days by the subsequent administration of 5 and 95 micrograms of GnRH 4 hours before the completion of each sampling period. Patients in ideal body weight and ovulatory cycles as well as five normal menstruating women included in the study for comparative purposes, were studied during the midluteal phase of a cycle. LH, oestradiol and progesterone were determined by radioimmunoassay. Areas under the LH curve were calculated by the trapezoid method; LH pulse detection was carried out by the program Cluster. Naloxone administration to patients with anorexia nervosa in the weight loss phase, did not significantly modify their serum LH levels nor the characteristics of its pulsatile secretion. Administration of the opioid blocker induced a significant increase in serum LH concentrations only in those patients in ideal body weight and amenorrhoea who resumed ovulatory cycles within the 6 months following the last study as well as in patients with an ideal body weight and ovulatory cycles and in normal controls. All patients and subjects who responded to naloxone administration exhibited significant increases in the area under the LH curve, mean LH pulse amplitude and peak area. Patients in ideal body weight and amenorrhoea who did not resume ovulatory cycles within the 6 months following the study days, did not respond to naloxone administration. There were no significant correlations between the magnitude of LH response to naloxone administration and the baseline levels of serum oestradiol and progesterone. All patients exhibited significant pituitary LH responses to both GnRH doses, regardless of the stage of the disease; however, the pituitary responsiveness shown by patients in ideal body weight was significantly higher than that presented by patients in weight loss. There were no significant differences between the responses to GnRH exhibited by patients in ideal body weight and amenorrhoea who responded to naloxone administration and those shown by patients in the same clinical condition but who were insensitive to opioid blockade. The re-establishment of hypothalamic-opioid inhibitory activity involved in LH secretion in patients with anorexia nervosa during the phase of weight gain predicts imminent restoration of ovulatory cycles. Pituitary LH response to exogenous GnRH during weight recovery does not accurately predict the outcome of the disease regarding reinitiation of menstrual cycles; however, it might be an indicator that the normal function of the hypothalamic-pituitary axis is being restored.

Effect of cyclosporin treatment on luteinizing hormone and prolactin

The effect of cyclosporin A (CsA) treatment on LH and prolactin was investigated. Chronic daily administration of an immunosuppressive dose of CsA (1.5 mg/100g bw) increased serum LH concentrations and pituitary gland LH content. CsA treatment also resulted in increased serum testosterone. Immunosuppressive doses of CsA had no effect on serum prolactin or pituitary gland prolactin content. Acute administration of low doses of 0.12, 1.2, 12 and 120ug CsA/100g bw had no effect on serum LH or prolactin. These results suggest that administration of immunosuppressive doses of CsA alters serum and pituitary LH and serum testosterone but not prolactin.

Changes in the responsiveness of luteinizing hormone secretion to infusion of the opioid antagonist naloxone throughout male sexual maturation.

The present study investigated the time of male sexual maturation during which hypothalamic inhibitory opioid activity can be detected. Normal prepubertal (Tanner stage G 1 (Ts-G1) (n = 4], early pubertal (Ts-G2 (n = 5], pubertal (Ts-G3 (n = 4), and Ts-G4 (n = 2] and adult subjects (Ts-G5 (n = 4] receives a rapid infusion of the selective opiate antagonist nalocone (NAL) (20 mg over 10 min). LH secretion was assessed by frequent (every 10 min for 2 h) venous sampling before and after administration of the opiate blocker, as well as by the LH response to exogenous GnRH. All but one (a Ts-G2 subject) pubertal boys showed aprompt and sustained increase in serum LH concentrations after NAL administration, as disclosed by the areas under the LH curve (aLHc) calculated from samples obtained before and after NAL infusion (aLHc in four Ts-G2 responders, 162 +/- 20 (mean +/- SEM) vs 314 +/- 56 mIU/ml/min before and after NAL respectively, P less than 0.025; Ts-G3, 227 +/- 35 vs 362 +/- 56 mIU/ml/min, P less than 0.025; Ts-G4 and Ts-G5, 432 +/- 77 vs 687 +/- 91 mIU/ml/min, P less than 0.05). In contrast, none of the prepubertal children had significant changes in LH secretion after the NAL challenge (154 +/- 17 vs 154 +/- 9 mIU/ml/min). Although all NAL responders exhibited serum testosterone (T) levels above 5 nmol/l, a positive correlation between individual T values and magnitude of LH responses to NAL was not found. All subjects had significant serum LH increments after GnRH administration. In a second series of studies, additional groups of Ts-G1 subjects were primed during 5 days either with GnRH alone or with GnRH plus sex steroids (ethinyl oestradiol 12.5 micrograms/12 h or testosterone enanthate 1.8 mg/kg body weight (single dose], before NAL administration, to investigate whether hypothalamic opioid activity might be unmasked by additional sex steroids. None of the priming schemes significantly modified the pituitary LH responses to NAL infusion (GnRH-primed group, 145 +/- 48 vs 139 +/- 43 mIU/ml/min before and after NAL, respectively; GnRH plus ethinyl oestradiol-primed group, 124 +/- 42 vs 107 +/- 34 mIU/ml/min; GnRH plus testosterone enanthate-primed group, 64 +/- 10 vs 57 +/- 24 mIU/ml/min). This study suggests that the development and/or maturation of the opioid control of LH secretion is temporally related with the onset of puberty.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of treatment with the opioid antagonists naloxone and naltrexone on LH secretion and on sexual maturation in immature female rats.

The effects on sexual maturation of the opioid receptor antagonists naloxone and naltrexone were studied in the female rat. Neonatal treatment (days 1-10) with either naloxone (2.5 mg/kg at 6-h intervals) or naltrexone (20 or 50 mg/kg per day) did not advance sexual maturation as judged by age and body weight at vaginal opening and first ovulation. After treatment with naltrexone (20 mg/kg) first ovulation occurred 2.3 days earlier than in saline-treated control rats but this could be attributed to a growth-stimulating effect of naltrexone; the effect was not observed with 50 mg/kg. An effect of neonatal treatment with naloxone on serum LH levels was seen at 23 days of age (155 +/- 36 (S.E.M.) vs 14 +/- 4 micrograms LH/l in controls, P less than 0.01), but not at 29 or 33 days of age, at 2 days before first ovulation nor at first pro-oestrus. There were no differences in the number of ova released at first oestrus, nor in the length of the first cycle. Neonatal treatment with naltrexone (50 mg/kg per day) did not alter the response to treatment with human chorionic gonadotrophin at 28-31 days of age: ovulation of a mean of 7.3 ova was induced on day 32 in both naltrexone- and saline-treated rats. Naltrexone treatment (four daily injections of 20 mg/kg at 2-h intervals) at 28-32 days of age advanced first ovulation by 4.4 days in about 40% of the rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Gonadotropin-Releasing Hormone is Required for Enhanced Luteinizing Hormone Subunit Gene Expressionin Vivo

Pre- and postcastration changes in LH beta and common alpha mRNAs were correlated with pituitary and serum LH levels in two different species after abolition of pituitary stimulation by GnRH. A GnRH antagonist (GnRH-ANT) was used to block gonadotroph GnRH receptors in male rats, and a GnRH antiserum (GnRH-AS) was used to inhibit GnRH stimulation of female and male mouse and male rat pituitaries. The postcastration increases in LH beta and common alpha mRNA levels (2- and 3.5-fold, respectively) were abolished in male rats after 7 days of continuous GnRH-ANT infusion. The postcastration increases in LH beta and common alpha mRNA in female (1.9- and 2.2-fold respectively) and male mice (1.4- and 3.6-fold, respectively) were also prevented after daily sc injection of GnRH-AS, as were the rises in LH beta (3-fold) and common alpha (4-fold) in castrated male rats. The pituitary LH content (postgonadectomy) was no different from intact control levels in all experimental animals regardless of treatment, while the increase in serum LH concentration in rats (7- and 8-fold) and in female (4.8-fold) and male mice (9.8-fold) was prevented by both GnRH-ANT and GnRH-AS administration. In intact rats treated with GnRH-ANT the LH beta mRNA level decreased (57%) while the common alpha mRNA level was unaffected after 7 days. Neither pituitary nor serum LH levels were altered in intact rats or mice after appropriate treatments. We conclude that endogenous GnRH is required for the postcastration rise of both LH beta and common alpha-subunit mRNA levels in rats and mice.

Relationships between training volume, physical performance capacity, and serum hormone concentrations during prolonged training in elite weight lifters.

A follow-up study of 1 year was performed on 11 male elite weight lifters. Several parameters including training volume, weight lifting performance, and serum hormone concentrations were measured during seven test occasions. In addition, the same measurements were repeated three times during a 6-week period preceding the primary competition, which took place about 5 months after beginning of the follow-up. The primary findings were observed during the 6-week period from which the first 2 weeks of stressful training was associated with significant decreases (P less than 0.01-0.001) in serum testosterone concentration, in testosterone/cortisol and in testosterone/SHBG ratios, and with a significant (P less than 0.001) increase in serum LH concentration. The individual changes during the stressful training in serum testosterone/SHBG ratio were related (r = .63; P less than 0.05) to the individual changes in the weight lifting result in the clean and jerk lift. During the following "normal" 2-week and reduced 2-week training periods, the concentration of serum testosterone remained unaltered, but serum cortisol and serum LH decreased significantly (P less than 0.05-0.01). During these periods, the serum testosterone/SHBG ratio increased (P less than 0.01). The individual changes during this preparatory 4-week training before the primary competition in serum testosterone/SHBG ratio and the individual changes in the weight lifting result in the clean and jerk lift correlated significantly with each other (r = .68; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Naloxone-induced secretion of LH in the male Syrian hamster: modulation by photoperiod and gonadal steroids.

The role of endogenous opiates in the regulation of photoperiodically induced testicular regression was studied in the male Syrian hamster. In reproductively active hamsters exposed to a long photoperiod (LD; 16 h light: 8 h darkness) or to short days (SD; 8 h light: 16 h darkness) for 20 weeks or to SD after pinealectomy, administration of naloxone, a competitive opiate receptor antagonist, at doses of 2.5-20 mg/kg, significantly increased serum LH concentrations. In marked contrast, these doses of naloxone did not produce any change in LH levels in reproductively quiescent hamsters exposed to SD for 8 weeks. The influence of gonadal steroids on the LH response to naloxone was studied in hamsters castrated or castrated and implanted s.c with a capsule containing testosterone. Naloxone did not induce LH release in castrated hamsters maintained in LD or in SD, but this response was restored in LD but not SD when serum testosterone concentrations were maintained at levels similar to those observed in intact reproductively active hamsters. These results show that inhibition of reproduction by the photoperiod prevents naloxone-induced LH release in the male hamster. This lack of response to naloxone is not due, however, to the lower testosterone titres present in these animals compared with reproductively active animals. Responsiveness to naloxone can be restored when the animal is rendered insensitive to the inhibitory photoperiod either by removal of the pineal gland or by induction of photorefractoriness by extended exposure to SD.