Basal LH Levels Research Articles

Endocrine profiles and semen quality in spinal cord injured men

To evaluate the hypothalamic-pituitary-testis (HPT) axis, endocrine profiles and semen quality in men with spinal cord injury (SCI). Fifty-five men with SCI were studied. Serum levels of FSH, LH, testosterone, oestradiol and prolactin (PRL) were determined; the LH-releasing hormone (LHRH) stimulation test and a semen analysis were performed, and testicular volumes were measured. Thirty-six age-matched healthy male volunteers and 34 noninjured infertile men served as controls. Eight SCI subjects had low basal LH, four had low basal FSH, and 16 had decreased basal serum levels of LH and FSH. Of subjects with lower serum levels of gonadotrophins (LH and/or FSH), nine had low serum testosterone and seven had hyperprolactinaemia. Serum levels of oestradiol were similar for all groups. There were increased LH and FSH responses to LHRH in SCI subjects compared to normal controls, but this difference was only statistically significant in SCI subjects with lower than normal serum levels of LH and/or FSH. There was no significant difference in testis volume between SCI subjects and controls. The mean semen volume in SCI subjects was lower than from controls, but the difference was not statistically significant. Sperm motility and percent normal sperm morphology were lower in SCI compared to normal controls but not to infertile control subjects. In total, 51% and 86% of SCI subjects had at least one hormonal or axis abnormality, respectively. We conclude that hypogonadotropism in SCI subjects is likely to be secondary to altered neural or hormonal pathways between the hypothalamus and the pituitary gland, and that these endocrine abnormalities may be the mechanisms contributing to impairment of semen quality.

Clinical and endocrine follow-up of patients after testicular sperm extraction

ObjectiveTo evaluate the risk of testicular damage from testicular biopsies that are carried out for testicular sperm extraction (TESE) in infertile men. DesignProspective controlled clinical study. SettingAcademic hospital. Patient(s)Forty infertile males with azoospermia. Intervention(s)Examination of the clinical, endocrine, biochemical, and sonographic data in average after 18 months after TESE was performed. Main outcome measure(s)Measurements before and after TESE: hormone values, testicular size, morphologic characteristics, and power Doppler after scrotal sonography. Result(s)Comparison of preoperative and postoperative values of basal testosterone, FSH, LH, and estradiol levels did not reveal any differences. Twelve of 26 patients had subnormal testosterone values before TESE; 14 of 39 patients had subnormal levels afterward. Postoperative sonographic measurements showed no significant difference of the testicular volume as compared with the preoperative values. Results of power Doppler sonography revealed pathological conditions (n = 5) in patients with former iliacal or testicular operations. Conclusion(s)Endocrine testicular function and testicular size were not impaired after testicular biopsy when compared with preoperative data. However, patients with nonobstructive azoospermia seem to be at risk for androgen deficiency due to primary testicular failure after repeated testicular biopsies.

Propriétés antigonadotropes d'un progestatif norprégnane : l'exemple du nomégestrol acétate

The antigonadotropic activity of progestins, progesterone and 19-norprogesterone derivatives, is generally used in clinical practice to treat hyperestrogenic symptoms and to provide a contraceptive effect in women with intolerance to exogenous estrogens. Our purpose was to review data from clinical pharmacological trials and from efficacy and/or safety clinical studies on progestin antigonadotropic properties with the example of nomegestrol acetate administered at the dose of 5 mg daily during 20 or 21 days per cycle. The antigonadotropic effect was shown by the effect on gonadotropins: in normally cycling premenopausal women, gonadotropin ovulatory peak was constantly inhibited, LH secretion was decreased and FSH increase at the end of the control cycle was inhibited by nomegestrol acetate ( n = 5). Moreover, LH basal levels, LH response to exogenous GnRH and aeras under the curves (AUC) of LH pulsatile profile were decreased in the treated cycle ( n = 11) compared to the control cycle. For both LH and FSH, the basal levels, the response to GnRH and the AUC of pulsatile profile were decreased by nomegestrol acetate compared to placebo in postmenopausal women; moreover, the frequency but not the amplitude of LH pulses was decreased. Depending on the woman's ovarian functional status, the effects of nomegestrol acetate on FSH were divergent (FSH increased before menopause and decreased at postmenopause), perhaps due to experimental conditions or a direct effect on the ovary. In postmenopausal women, the action of nomegestrol acetate on gonadotropin secretion was not modified by flutamide, a pure antiandrogen; this suggests that the antigonagotropic activity of the progestin is not mediated through the androgen receptor and it acts probably through the progesterone receptor. This antigonadotropic effect had an impact on ovarian function: in premenopausal women on nomegestrol acetate ( n = 21), progesterone secretion was inhibited attesting to the absence of corpus luteum, the pre-ovulatory peak of estradiol was inhibited and plasma estradiol concentrations were decreased. The antigonadotropic activity of nomegestrol acetate results in reinforcement of its antiestrogenic activity, particurlarly on the endometrium and enables to treat the frequent clinical hyperestrogenic symptoms of the perimenopause without negative metabolic or hemostatic effects. In the efficacy and/or safety studies, no pregnancy was observed with nomegestrol acetate administered in antigonadotropic sequence, during 1355 treated cycles and the hormonal data ( n = 205) were in agreement with the antigonadotropic effects of the progestin demonstrated in the clinical pharmacological studies. Furthermore, at the same dose and sequence, nomegestrol acetate, in addition to its inhibitory effect on ovulation, induces changes in the endometrium rendering it unable to implantation and in the cervical mucus to rendering it hostile to spermatozoa migration. However, it must be emphasized that data from experimental conditions required for the calculation of the Pearl Index are not available and therefore there is no legal claim for “contraception”.

Reproductive endocrinology and postweaning performance in the multiparous sow: Part 2. Influence of nursing behavior

The reason for variation in postweaning reproductive performance among multiparous sows is to a large extent unknown. In the present study, the influence of nursing behavior was explored. Blood samples were collected during lactation and after weaning from 18 multiparous sows for cortisol, LH, estradiol-17β (E2), and progesterone analysis. Sow and piglet behavior was videotaped. The sows were fed according to litter size and slaughtered after the second postweaning estrus. The sows were divided into two groups based on average values for the different behavioral parameters. Sows with a long average nursing duration (long group) had lower average and basal LH levels on Day 14 and 21 of lactation as compared to the sows having a short average nursing duration (short group). In the long group, concentrations of E2 were lower the day after weaning, but on Day 15 and 21 of lactation no differences were noted between the two groups. Postweaning performance seemed impaired in the long group, though, differences were not significant. The sows in the long group were heavier and tended to lose less weight during lactation. To conclude, nursing duration seems to influence the extent to which reproductive functions are inhibited during lactation.

Prognostic value of the clinical and laboratory evaluation in patients with nonmosaic Klinefelter syndrome who are receiving assisted reproductive therapy

Objective: To characterize clinical and laboratory findings in nonmosaic 47,XXY patients that may help to predict spermatogenetic activity in their testicles. Design: Prospective study. Setting: Assisted reproductive technology program. Patient(s): Twenty patients with nonmosaic Klinefelter syndrome who underwent testicular sperm retrieval for IVF. Main Outcome Measure(s): The correlation between basal FSH, LH and testosterone levels, mean testicular volume, and results of the hCG test and presence or absence of sperm after testicular sperm extraction (TESE). Result(s): Sperm was found in nine patients (45%). The mean testicular volume was 7.8 ± 2.5 mL in men with sperm after TESE and 5.6 ± 1.2 mL in those without sperm after TESE; corresponding testosterone levels were 3.5 ± 1.2 ng/mL and 1.7 ± 0.8 ng/mL. Serum levels of FSH and LH did not significantly differ between groups. After the hCG test, the mean serum testosterone level was 16.0 ± 6.3 ng/mL in men with sperm after TESE and 6.7 ± 5.6 ng/mL in those without sperm. Conclusion(s): Testicular volume, testosterone levels, and results of the hCG test are important predictive factors of spermatogenesis in patients with nonmosaic Klinefelter syndrome.

Effect of long-term naltrexone treatment on endocrine profile, clinical features, and insulin sensitivity in obese women with polycystic ovary syndrome

Objective: Evaluation of clinical and endocrine effects of naltrexone administration in obese women with PCOS. Design: Open, controlled, clinical study. Setting: Department of Reproductive Medicine and Child Development, Section of Gynecology and Obstetrics, University of Pisa, Pisa, Italy. Patient(s): Ten PCOS women were studied. Intervention(s): Women were treated with naltrexone (50 mg/day) for 6 months. Main Outcome Measure(s): Body mass index and the menstrual cyclicity during naltrexone treatment were assessed. Basal levels of LH, FSH, 17β-estradiol (E 2), 17-hydroxyprogesterone, total and free T, androstenedione, dehydroepiandrosterone sulfate, cortisol, sex hormone-binding globulin were evaluated before treatment and every 3 months. Progesterone levels were measured in the luteal phase during the sixth month. Gonadotropin response to GnRH administration (10 μg) and a 75-g oral glucose tolerance test were performed before and every 3 months. Result(s): Body mass index significantly decreased from 29.94 ± 1.04 to 26.07 ± 0.81 during treatment. The menstrual cyclicity improved in 80% of PCOS women: the mean cycle length was 40–360 days before treatment and ranged between 25 and 120 days and 28–120 days after 3 and 6 months of treatment. Plasma levels of free T, androstenedione, dehydroepiandrosterone sulfate, and cortisol significantly decreased. Fasting glucose-to-insulin ratio improved in women with insulin resistance. Conclusion(s): Naltrexone may have a beneficial effect on the clinical and endocrine-metabolic disturbances of obese PCOS women. Whether these effects are the consequences of weight loss or are due to changes in opioidergic tone is debatable.

Leuteinizing hormone responses to leuprolide acetate discriminate between hypogonadotropic hypogonadism and constitutional delay of puberty

Objective: To assess if leuprolide acetate stimulation discriminates between hypogonadotropic hypogonadism (HH) and constitutional delay of puberty (CDP) in males. Design: Case-control study. Setting: Patients attending an academic research environment. Patients: Only male patients were studied: 10 with HH (group 1, age 16.5 ± 6.0 years), 8 prepubertal with CDP (group 2, age 14.3 ± 1.2 years), 6 healthy prepubertal (group 3, age 9.5 ± 3.3 years), and 8 healthy late-pubertal (group 4, age 15.1 ± 3.1 years). Intervention(s): Blood samples were obtained after an overnight fast. Leuprolide acetate was then administered SC, and blood samples were drawn at 0, 30, 60, 120, 180 minutes, and 6 and 24 hours after stimulation. Main Outcome Measure(s): Clinical follow-up evaluations of data and serum levels of LH, FSH, 17-hydroxyprogesterone, and testosterone. Result(s): Basal LH levels were similar in groups 1 through 3 and differed significantly from those in group 4. Peak serum LH levels were significantly higher in CDP compared with HH (8.9 ± 1.4 vs. 1.4 ± 0.2 IU/L). Baseline FSH levels were significantly higher only in pubertal boys (versus the HH group); peak levels did not differ among the groups. Basal and peak testosterone levels were significantly higher only in the control pubertal group when compared to the other groups; peak 17-hydroxyprogesterone concentrations were significantly higher in pubertal controls compared with HH and CDP. Conclusion(s): Peak LH responses clearly discriminate HH from CDP. Timing for blood sampling should be fixed at 0, 60, 120, 180 minutes after stimulation.

Basal ultrasensitive LH assay: a useful tool in the early diagnosis of male pubertal delay?

The aim of this study was to evaluate the usefulness of basal measurements of gonadotropins in distinguishing between constitutionally delayed puberty (DP) and hypogonadotropic hypogonadism (HH), comparing its diagnostic efficiency with that of the dynamic GnRH infusion test (0.83 microg/min during 120 min). We studied 20 males, chronological age (CA) 14-18 years, with a final diagnosis of DP (n = 8), partial HH (n = 5) and complete HH (n = 7), confirmed by follow-up. We also evaluated basal samples of ultrasensitive LH and FSH in 117 healthy control males (CA 2-19 yr), classified according to Tanner stage. In the control group, ROC plot analysis showed a cutoff to differentiate prepuberty from puberty of 0.65 IU/l for LH (sensitivity: 91%, specificity: 98%). Differences were found (p < 0.05) in basal LH and in maximal responses to GnRH in complete HH in relation to DP and partial HH. The diagnostic efficiency of the GnRH infusion test was 85%. For basal LH, a cut-off limit of 0.65 IU/l showed a diagnostic efficiency of 85% for complete HH and 100% for partial HH and DP. We conclude that, in our experience, basal LH levels above 0.65 IU/l measured by ultrasensitive assay would rule out a complete deficiency. It was not possible to differentiate DP from partial HH, either in basal samples or with the infusion test.

Precocious puberty: clinical and endocrine profile and factors indicating neurogenic precocity in Indian children.

The objective of this study was to evaluate the clinical and endocrine profile of patients with precocious puberty followed up in a tertiary care hospital. Records of 140 patients (114 girls, 26 boys) with precocious puberty were reviewed. Clinical features including age of onset, stage of pubertal development, presenting symptoms, features suggestive of CNS involvement and family history were analyzed. Endocrine investigations included basal and GnRH-stimulated levels of LH and FSH as well as 17OHP, DHEA, hCG and thyroid profile. Abdominal and pelvic ultrasonography and CNS imaging were correlated with clinical features. Girls outnumbered boys in this series (4.4:1). Neurogenic central isosexual precocious puberty (CIPP) was more common in boys (10 out of 18, 55.6%) than girls (16 out of 77, 20.8%). The most common cause of neurogenic CIPP was hypothalamic hamartoma present in five girls and four boys. Other causes of neurogenic CIPP included neurotuberculosis, pituitary adenoma, hydrocephalus, post radiotherapy, CNS tumors and malformations. Peripheral precocious puberty (PPP) was secondary to adrenal causes in boys and ovarian cysts in girls. Benign variants of precocious puberty, such as premature thelarche and premature adrenarche, were present in 23 and six girls, respectively. Hypothyroidism was present in four girls and McCune-Albright syndrome in one girl. Girls with neurogenic CIPP had a lower age of onset as compared to idiopathic CIPP (3.6 +/- 2.7 years vs 5.4 +/- 2.5 years, p = 0.014). The lowest age of onset was seen in girls with hypothalamic hamartoma (1.6 +/- 0.9 years). Forty-seven girls with CIPP (seven neurogenic and 40 idiopathic) presented after the age of 6 years. Features of CNS involvement, in the form of seizures, mental retardation, raised intracranial tension or focal neurological deficits, were present in seven girls (43.8%) and four boys (40%), and gelastic seizures were present in three children. Girls with CIPP had greater bone age advancement (3.4 +/- 1.5 years) and negative height standard deviation for bone age (-2.7 +/- 1.5) than those with PPP (1.9 +/- 1.6 years and -1.3 +/- 1.3) and premature thelarche (0.4 +/- 0.4 years and -0.8 +/- 0.8). Patients with neurogenic CIPP had significantly higher levels of baseline and GnRH-stimulated levels of LH and FSH and LH:FSH ratio than those with idiopathic CIPP. Occurrence of neurogenic CIPP in seven girls with an age of onset after 6 years emphasizes the need for CNS imaging in these girls contrary to the current recommendations. The fact that 65.6% cases of idiopathic CIPP presented after the age of 6 years raises the possibility that these patients may be physiological variants of normal puberty. Pointers to neurogenic CIPP included early age of onset in girls, clinical features of CNS involvement, and elevated basal and stimulated LH levels and LH:FSH ratio.

Does controlled ovarian stimulation (COS) in assisted reproductive technologies with recombined human FSH (r-hFSH) need the use of human menopausal gonadotropin (HMG)?

Objective: The suppression of the endogenous LH secretion after the use of a high dose of GnRH agonist in the common long luteal protocol and the advent of r-h FSH leads to a debate whether it is necessary to add or not exogenous LH during the COS. This study aims to compare the results of ovarian stimulation using r-h FSH alone versus the combination of r-h FSH and the HMG, in order to determine the threshold of the basal level of LH, after down regulation, that would allow to predict if the COS needs LH supplementation to obtain a correct follicular growth, and an appropriate steroidogenesis.

Two novel mutations in the gonadotropin-releasing hormone receptor gene in Brazilian patients with hypogonadotropic hypogonadism and normal olfaction.

Several point mutations in the GnRH receptor gene have been described in an autosomal recessive form of congenital isolated hypogonadotropic hypogonadism (HH). We investigated 17 Brazilian patients (10 males and 7 females) from 14 different families, with HH and normal olfaction. The diagnosis of HH was based on absent or incomplete sexual development after 17 yr of age associated with low or normal levels of LH in both sexes and low levels of testosterone in males and of estradiol in females. All patients presented with a normal sense of smell in an olfactory specific test. The coding region of the GnRH receptor gene was amplified by PCR and directly sequenced. A novel missense mutation, Arg(139)His, located in the conserved DRS motif at the junction of the third transmembrane and the second intracellular loop of the GnRH receptor was identified in the homozygous state in one female with complete HH. The Arg(139)His mutation completely eliminated detectable GnRH-binding activity and prevented GnRH-induced stimulation of inositol phosphate accumulation in vitro. In another family, a new compound heterozygous mutation (Asn(10)Lys and Gln(106)Arg) was identified in four siblings (two males and two females) with partial HH. The Gln(106)Arg mutation, located in the first extracellular loop, has been previously described, and in vitro analysis indicated that the mutant receptor was able to bind GnRH, but with a reduced affinity. The Asn(10)Lys mutation in the extracellular amino-terminal domain of the receptor also reduced the affinity for GnRH in vitro. In this family we also identified a previously described silent polymorphism at amino acid residue 151 in the second intracellular loop that segregated with the two inactivating mutations of the GnRH receptor. This polymorphism was also found in two unrelated patients with sporadic HH without GnRH receptor loss of function mutations. No mutations were identified in the remaining cases. A good correlation between genotype and phenotype was found in our patients. The woman, who is homozygous for the completely inactivating Arg(139)His mutation, has complete HH with undetectable serum basal LH and FSH levels that failed to respond to GnRH stimulation. In addition, the affected patients who are compound heterozygotes for the Asn(10)Lys/Gln(106)Arg mutations, have partial HH with low serum basal LH levels that were responsive to GnRH stimulation. No clinical or hormonal differences were found between HH patients with and without mutations in the GnRH receptor gene, indicating that these data do not contribute to the identification of HH patients with GnRH receptor mutations. In conclusion, we report the first naturally occurring mutation within the conserved DRS motif of the GnRH receptor in a female with complete HH and a novel compound heterozygous mutation (Asn(10)Lys and Gln(106)Arg) in a family with partial HH, increasing the repertoire of the inactivating mutations of the GnRH receptor.

Alteration of gonadotrophin and steroid hormone release, and of ovarian function by a GnRH antagonist in gilts

This study examined the impact of the gonadotrophin-releasing hormone (GnRH) antagonist Antarelix™ on LH, FSH, ovarian steroid hormone secretion, follicular development and pituitary response to LHRH in cycling gilts. Oestrous cycle of 24 Landrace gilts was synchronised with Regumate ® (for 15 days) followed by 800 IU PMSG 24 h later. In experiment 1, Antarelix™ ( n=6 gilts) was injected i.v. (0.5 mg per injection) twice daily on four consecutive days from day 3 to 6 (day 0=last day of Regumate ® feeding). Control gilts ( n=6) received saline. Blood was sampled daily, and every 20 min for 6 h on days 2, 4, 6, 8 and 10. In experiment 2, gilts ( n=12) were assigned to the following treatments: Antarelix™; Antarelix™ + 50 μg LHRH on day 4; Antarelix™ + 150 μg LHRH on day 4 or control, 50 μg LHRH only on day 4. Blood samples were collected daily and every 20 min for 6 h on days 2, 4 and 6 to assess LH pulsatility. Ovarian follicular development was evaluated at slaughter. Antarelix™ suppressed ( P<0.05) serum LH concentrations. The amount of LH released on days 4–9 (experiment 1) was 8.80 versus 36.54 ng ml −1 (S.E.M.=6.54). The pattern of FSH, and the preovulatory oestradiol rise was not affected by GnRH antagonist. Suppression of LH resulted in a failure ( P<0.05) of postovulatory progesterone secretion. Exogenous LHRH (experiment 2) induced a preovulatory-like LH peak, however in Antarelix™ treated gilts the LH surge started earlier and its duration was less compared to controls ( P<0.01). Furthermore, the amount of LH released from day 4 to 5 was lower ( P<0.01) in Antarelix™, Antarelix™ + 50 and Antarelix™ + 150 treated animals compared to controls. No differences were estimated in the number of LH pulses between days and treatment. Pulsatile FSH was not affected by treatment. Mean basal LH levels were lower ( P<0.05) after antagonist treatment compared to controls. Antarelix™ blocked the preovulatory LH surge and ovulation, but the effects of Antarelix™ were reduced by exogenous LHRH treatment. The development of follicles larger than 4 mm was suppressed ( P<0.05) by antagonist treatment. In conclusion, Antarelix™ treatment during the follicular phase blocked preovulatory LH surge, while FSH and oestradiol secretion were not affected. Antarelix™ failed to alter pulsatile LH and FSH secretor or pituitary responsiveness to LHRH during the preovulatory period.

In vivo secretory potential and the effect of combination therapy with octreotide and cabergoline in patients with clinically non-functioning pituitary adenomas.

The secretory capacity, in vivo, of clinically non-functioning pituitary adenomas may possibly predict tumour volume reduction during intensive medical therapy. Ten patients (mean (range) 53 years (26-73)) with clinically non-functioning macroadenomas, > or = 10 mm were studied. The secretory capacity of the adenomas was examined using basal, NaCl and TRH-stimulated LH, FSH and alpha-subunit levels. The effect on tumour volume of 6 months' therapy with the combination of a somatostatin analogue, octreotide 200 microg x 3/day and a dopamine-D2-agonist, cabergoline 0.5 mg x 1/day was studied. The basal LH, FSH and alpha-subunit levels were determined before and during 6 months' therapy with octreotide and cabergoline, and MR scans were used to evaluate tumour volume before and during this period of therapy. Octopus-perimetry was used to examine the visual fields. A reduction in tumour volume (mean +/- SEM (range); 30% +/- 4% (18-46%)) during 6 months of combination therapy with octreotide and cabergoline was recorded only in patients with in vivo secretory potential. Tumour volume was not reduced in four patients: in three of these patients it remained unchanged while in one patient it was observed to have increased (by 14%). Of the six patients with pretherapy secretory capacity, one displayed a very high basal level of alpha-subunit (74 microg/l) despite unmeasurable levels of LH and TSH, and an FSH-level of 1 IU/l. The other five patients presented paradoxical LH, FSH and/or alpha-subunit responses to TRH. A reduction in basal levels of LH, FSH and/or alpha-subunit was observed in all six patients, and the maximum reduction of at least one of the hormonal levels was 66% +/- 7% (50-98%). The basal levels of LH, FSH and alpha-subunit in the 10 patients were (mean +/- SEM (range)), 3.0 IU/l +/- 1.0 (0.0-7.4), 12.7 IU/l +/- 5.0 (0.0-39.0) and 9.0 IU/l +/- 7.0 (0.2-74.0). During six months of therapy with octreotide and cabergoline, the basal levels of LH, FSH and alpha-subunit were reduced by > or = 50% in seven patients - including the six patients with in vivo secretion prior to therapy. No new visual field defects were detected during therapy and no deterioration of existing visual field defects was recorded. The medical therapy was well tolerated. The in vivo basal and TRH-stimulated secretory capacity of LH, FSH and alpha-subunit predicted tumour reduction following intensive medical therapy in all of our patients with non-functioning pituitary adenomas.

Is an elevation in basal follicle-stimulating hormone levels in unexplained infertility predictive of fecundity regardless of age?

An elevation in follicle-stimulating hormone (FSH) levels is considered to reflect lowered ovarian function, resulting in poor fecundity in infertile women. However, it remains to be clarified whether or not the significance of FSH levels applies equally to all women irrespective of age. The objective of the present study is to compare basal FSH levels in infertile women who conceived or not after stratification by age. A total of 144 infertile women between ages 25 and 45 who underwent infertility treatment due to unexplained infertility in the University of Tokyo Hospital were included in the retrospective study. Subjects were divided by age into two groups, < 38 (n=98) vs > or = 38 (n=46) years, with ages ranging from 25 to 37, and from 38 to 45, respectively. Blood samples were collected in early follicular phase (day 4-6) for assessment of basal levels of LH, FSH, and PRL. In the older group, pregnant cases had significantly lower FSH levels (6.07 +/- 2.83 mIU/ml) than nonpregnant cases (9.60 +/- 3.67 mIU/ml), whereas no difference in basal FSH levels was observed between pregnant and nonpregnant cases in the younger group. Basal FSH levels of pregnant cases in the older group were significantly lower than those of pregnant cases in the younger group (8.26 +/- 2.95 mIU/ml). Basal LH and PRL levels were not related to fecundity in either group. Thus, an increase in basal FSH levels as a predictor of fecundity should be considered in the context of age.

The effect of distinct activating mutations of the luteinizing hormone receptor gene on the pituitary-gonadal axis in both sexes.

Familial or sporadic male-limited precocious puberty is a distinct and unusual gonadotrophin-independent form of sexual precocity caused by constitutively activating mutations of the luteinizing hormone receptor (LHR). In the present study, we evaluated the effect of known activating mutations at different sites of the LHR gene on the pituitary-gonadal axis in both sexes. Four unrelated Brazilian boys (I-IV) with gonadotrophin-independent precocious puberty and two asymptomatic females (V-VI), a sister and mother of two of the affected boys, were studied. Patients I, II and V carried the Ala568Val mutation located at the third intracellular loop of the LHR. Patient III carried the Leu457Arg mutation at the third transmembrane helix, and patients IV and VI carried the Thr577Ile mutation at the sixth transmembrane helix of the LHR. Serum levels of LH, FSH, testosterone, and oestradiol under basal and GnRH-stimulated conditions were determined in all patients. Testosterone levels were also measured after a hCG stimulation test in patient III. Basal LH and FSH levels were prepubertal in all boys studied. The GnRH-stimulated serum LH and FSH levels were prepubertal in three boys (I, II and IV), whereas patient III showed totally suppressed LH and FSH levels at ages 2 and 7 years (bone ages 6 and 14 years, respectively). Serum testosterone levels ranged from 3.8 to 69.5 nmol/l in the four boys. Patient III had the highest testosterone levels that did not respond to hCG stimulation. The 4 year-old girl (patient V) was phenotypically normal and the acute response to GnRH was indicative of prepubertal status. Patient VI had normal menstrual cycles and fertility. These findings indicate variable effects of LHR activating mutations on the pituitary-gonadal axis in boys that can result in lack of normal LH and FSH release. In contrast, prepubertal and adult females were asymptomatic and had normal basal and GnRH-stimulated LH and FSH levels.

Pudu, the smallest deer of the world: 10 years of endocrine studies of Southern Pudu (Pudu puda) in Chile

The first ten years of research on pudu physiology and behavior concentrated on the investigation of hormone profiles in males. Basic and seasonal levels of LH, FSH, testosterone, prolactin, IGF-1, cortisol and triiodothyronine were determined. The seasonal fluctuations of reproductive and other hormones are related to the reproductive and the antler cycles and the social rank of individual males. In addition, basal and poststimulatory levels of cortisol, growth hormone (GH), LH, FSH and testosterone were reported after ACTH and GnRH challenge tests. Most blood levels of hormones in male pudu are in the low range often less than half of hormonal levels of another small cervid, the roe deer. Pudu responds quickly to simulated stress and GnRH elicits a vigorous increase of LH and T in the dominant males. The next phase of our research is now concentrated on the reproductive physiology of the female pudu, where a delayed implantation of the embryo is suspected.

Mechanism for the development of ovarian cysts in patients with congenital lipoid adrenal hyperplasia

Although ovarian cysts commonly occur in patients with congenital lipoid adrenal hyperplasia (CLAH), the mechanism of development remains to be determined. To clarify the pathogenesis of the ovarian cysts, endocrinological examinations were performed in patients with CLAH. The subjects were three Japanese CLAH patients. Basal body temperature, serum and urinary gonadotropin levels, serum and/or urinary ovarian hormones and mutations of the steroidogenic acute regulatory protein (StAR) gene were examined. The basal body temperature was not biphasic in any patient. Basal LH levels were high in all CLAH patients and markedly responded to LH-releasing hormone in two patients. Urinary gonadotropin analysis revealed repetitive LH surges in the menstrual cycles of the CLAH patients. No increase in the urinary pregnanediol suggested anovulation in all patients, and bilateral ovarian cysts were found in two of the subjects. Examination of the StAR gene revealed a frameshift mutation 840delA at codon 238, a nonsense mutation Q258X at codon 258, a homozygotic mutation at Q258X, and a compound heterozygotic mutation with 251insG and Q258X. We concluded that the development of ovarian cysts may be derived from continued anovulation in CLAH patients. Elevated LH levels may be explained by increased sensitivity of the anterior pituitary to circulating estrogen.

Hypothalamic amenorrhea with normal body weight: ACTH, allopregnanolone and cortisol responses to corticotropin-releasing hormone test.

Hypothalamic amenorrhea (HA) is a functional disorder caused by disturbances in gonadotropin-releasing hormone (GnRH) pulsatility. The mechanism by which stress alters GnRH release is not well known. Recently, the role of corticotropin-releasing hormone (CRH) and neurosteroids in the pathophysiology of HA has been considered. The aim of the present study was to explore further the role of the hypothalamic-pituitary-adrenal axis in HA. We included 8 patients (aged 23.16+/-1.72 years) suffering from hypothalamic stress-related amenorrhea with normal body weight and 8 age-matched healthy controls in the follicular phase of the menstrual cycle. We measured basal serum levels of FSH, LH, and estradiol and evaluated ACTH, allopregnanolone and cortisol responses to CRH test in both HA patients and healthy women. Serum basal levels of FSH, LH, and estradiol as well as basal levels of allopregnanolone were significantly lower in HA patients than in controls (P<0.001) while basal ACTH and cortisol levels were significantly higher in amenorrheic patients with respect to controls (P<0.001). The response (area under the curve) of ACTH, allopregnanolone and cortisol to CRH was significantly lower in amenorrheic women compared with controls (P<0.001, P<0.05, P<0.05 respectively). In conclusion, women with HA, despite the high ACTH and cortisol levels and, therefore, hypothalamus-pituitary-adrenal axis hyperactivity, are characterized by low allopregnanolone basal levels, deriving from an impairment of both adrenal and ovarian synthesis. The blunted ACTH, allopregnanolone and cortisol responses to CRH indicate that, in hypothalamic amenorrhea, there is a reduced sensitivity and expression of CRH receptor. These results open new perspectives on the role of neurosteroids in the pathogenesis of hypothalamic amenorrhea.

Diagnostic value of fluorometric assays in the evaluation of precocious puberty.

To establish normative data and determine the value of fluorometric AutoDELFIA assays (Wallac Oy) in the investigation of precocious puberty, we determined serum levels of LH, FSH, testosterone, and estradiol under basal and GnRH-stimulated conditions in 277 normal subjects at various pubertal stages and in 77 patients with precocious puberty. A substantial overlap was observed in basal and GnRH-stimulated gonadotropin levels in normal individuals of both sexes with pubertal Tanner stages 1 and 2. The 95th percentile of the normal prepubertal population was the cut-off limit between prepubertal and pubertal levels. These limits were 0.6 IU/L in both sexes for basal LH, 9.6 IU/L in boys and 6.9 IU/L in girls for peak LH after GnRH stimulation, 19 ng/dL in boys for basal testosterone, and 13.6 pg/mL in girls for basal estradiol. Basal and peak LH exceeding these limits were considered positive tests for the diagnosis of gonadotropin-dependent precocious puberty. According to these criteria, the sensitivities of basal and peak LH for the latter diagnosis were 71.4% and 100% in boys, and 62.7% and 92.2% in girls. The specificity and positive predicted value were 100% in both sexes for basal and peak LH levels. The negative predicted values for basal and peak LH were 62.5% and 100% in boys, and 40.6% and 76.5% in girls. Basal and GnRH-stimulated FSH levels overlapped among the various pubertal stages in normal subjects and were, in general, not helpful in the differential diagnosis of precocious puberty. In conclusion, basal LH levels were sufficient to establish the diagnosis of gonadotropin-dependent precocious puberty in 71.4% of boys and 62.7% of girls. In the remaining patients, a GnRH stimulation test was still necessary to confirm this diagnosis. Finally, suppressed LH and FSH levels after GnRH stimulation indicate gonadotropin-independent sexual steroid production.

An Analysis of Physiological Mechanisms Underlying the Antigonadotropic Action of Intracranial Prolactin in Ring Doves

Intracerebroventricular (ICV) injections of prolactin (PRL) exert potent antigonadal and antigonadotropic effects in ring doves (Streptopeliarisoria) at doses that are insufficient to stimulate prolactin-dependent crop growth. To explore the physiological basis of these effects, we tested the ability of ICV-injected PRL to influence pituitary responsiveness to chicken gonadotropin-releasing hormone-I (cGnRH-I) and to alter GnRH content and concentration in the preoptic area (POA) and median eminence (ME). cGnRH-I-induced changes in plasma LH were monitored by radioimmunoassay (RIA) in photostimulated male doves after they received five daily ICV injections of ovine PRL (1 μg/2 μl) or saline vehicle. Although PRL treatment reduced basal plasma LH levels and testes weight, it did not reduce the amount or alter the pattern of LH released in response to a bolus injection of cGnRH-I. This suggests that ICV PRL does not suppress LH by reducing pituitary responsiveness to GnRH. In two subsequent studies, GnRH content (ng/region) and concentration (pg/μg protein) in the POA and ME were measured in male doves by RIA and by competitive enzyme immunoassay after 5 days of ICV PRL or vehicle treatment. Although ICV PRL reduced plasma LH levels in both studies, no significant PRL-induced alterations in GnRH content or concentration were apparent. In a final study, PRL-treated female doves had lower plasma LH levels than vehicle-treated control females at 12 and 24 h after a single ICV injection. GnRH content of the POA was also lower in PRL-treated females than in controls at 24 h. However, the two treatment groups did not differ in POA or ME GnRH content at earlier postinjection sampling intervals. Analysis of GnRH concentration data revealed no treatment group differences in either region at any sampling interval (1, 6, 12, or 24 h post-PRL injection). Collectively, these results are consistent with the idea that ICV-injected PRL acts at the level of the CNS to inhibit the reproductive system. However, the nature of the alterations involved remains to be clarified. Plausible hypotheses are (1) that ICV PRL suppresses the gonadal axis by influencing the activity of GnRH neurons at brain sites other than the POA or ME or (2) that PRL alters the synthesis, storage, degradation, and/or release of GnRH in the POA or ME, but the dynamic changes involved are not reflected in integrated, steady-state measures such as peptide content or concentration in tissue.