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PubMed2000

Central inhibition of gonadotropin-releasing hormone secretion in the growth-restricted hypogonadotropic female sheep.

Growth retardation induced by dietary restriction results in hypogonadotropism, and thus, puberty is delayed. The present studies determined 1) whether reduced LH secretion in the growth-retarded condition is due to a reduction in the frequency and/or in the amplitude of GnRH secretion, and 2) whether the mechanism regulating LH secretion is being actively inhibited via central mechanisms. To determine whether GnRH pulse frequency and/or amplitude are reduced during growth restriction, blood samples were simultaneously collected from pituitary portal blood for GnRH and from jugular blood for LH determinations over a 4-h period in ovariectomized lambs (52 wk of age) that were either growth restricted (28 kg; n = 8) or growing normally (60 kg; n = 7). As expected, the growth-restricted females were hypogonadotropic and exhibited a long LH interpulse interval compared with the normally growing females. However, although the GnRH interpulse interval was longer in the growth-restricted lambs compared with that in the normally growing lambs, the pattern of GnRH secretion did not directly correspond with that of LH secretion in the growth-restricted group. In addition, high amplitude GnRH pulses that coincided with LH pulses and small, low amplitude GnRH pulses without a concomitant LH pulse occurred. The second study tested the hypothesis that diet-induced hypogonadotropism is the result of actively inhibited central mechanisms by investigating the effects of the nonspecific central nervous system inhibitor, sodium pentobarbital, on pulsatile LH secretion in the growth-restricted lamb. Serial blood samples were collected from 11 ovariectomized lambs that were maintained at weaning weight (approximately 20 kg) by reduced diet. After a 4-h pretreatment period, six of the lambs were anesthetized with sodium pentobarbital for 4 h; the other five lambs were untreated and served as controls. Pentobarbital anesthesia reduced the LH interpulse interval (increased the frequency) and increased mean LH levels. These findings suggest that during growth restriction hypogonadotropism arises from a central inhibition of GnRH neurons and is manifest as a decrease in both frequency and amplitude of GnRH pulses.

Activity Cycles↗
PubMed2003

Effects of suppression of estrogen action by the p450 aromatase inhibitor letrozole on bone mineral density and bone turnover in pubertal boys.

The essential role of estrogen (E) in regulation of developing peak bone mass in males was confirmed when young adult men were described who cannot respond to or produce E because of defective E receptor alpha or P-450 aromatase enzyme, respectively. These men had significantly reduced bone mineral density (BMD) despite normal or supranormal androgen concentrations, and E administration improved BMD in the men with aromatase deficiency, whereas testosterone (T) was ineffective. Because new P450 aromatase inhibitors may prove to be potential drugs in various growth disorders, the effect of suppression of E action on developing peak bone mass has to be closely evaluated. In this study, we explored the effects of suppression of E synthesis on bone metabolism in pubertal boys. A total of 23 boys with constitutional delay of puberty were randomized to receive T and placebo or T and a specific and potent P450 aromatase inhibitor, letrozole. We determined BMD in the lumbar spine and the femoral neck. Bone resorption was studied by measuring the serum concentration of cross-linked carboxyterminal telopeptide of type I collagen by two different methods (CTx and ICTP), and bone formation by determining the serum concentrations of carboxyterminal propeptide of type I procollagen (PICP), osteocalcin, and alkaline phosphatase. We demonstrated previously that, during treatment with T and placebo, the concentrations of androgens and E increased. During treatment with T and letrozole, the E concentrations remained at the pretreatment level, but the androgen concentrations increased; the increase in the T concentration was more than 5-fold higher than during treatment with T and placebo. We did not observe any significant differences in the changes in bone mineral content, BMD, or bone mineral apparent density, an estimate of true volumetric BMD, between the treated groups. Lumbar spine bone mineral apparent density increased in both treated groups; but in the T- plus letrozole-treated group, the increase was statistically significant only 6 months after discontinuation of letrozole treatment. All bone resorption and formation markers increased during treatment with T and placebo. During treatment with T plus letrozole, CTx, PICP, and osteocalcin remained unchanged, whereas ICTP and alkaline phosphatase increased. Thus, 1-yr treatment with this new P450 aromatase inhibitor in pubertal boys is unlikely to be associated with any major harmful effect on developing peak bone mass. However, to convincingly exclude such effects, particularly rare or minor ones, will require a study with a larger sample size; and thus, close follow-up of bone metabolism during treatment with P450 aromatase inhibitors is still warranted.

Adolescent↗
PubMed2005

A window of opportunity: the diagnosis of gonadotropin deficiency in the male infant.

A common cause of micropenis is congenital hypogonadotropic hypogonadism, whether isolated or associated with multiple pituitary hormone deficiencies. The postnatal surge in FSH, LH, and testosterone in the male infant as a consequence of the continued function of the fetal GnRH pulse generator provides a 6-month window of opportunity to establish the diagnosis of hypogonadotropic hypogonadism and alert the clinician to the possibility of its association with multiple pituitary hormone deficiencies. When ACTH or GH deficiency or both deficiencies are present, hypoglycemia and cortisol deficiency can lead to neonatal and infantile death or increased morbidity. Establishing the diagnosis of hypogonadotropic hypogonadism in infancy preempts the uncertainties and delays in distinguishing constitutional delay in puberty from hypogonadotropic hypogonadism. Accordingly, hormone replacement therapy can be initiated at the normal age of pubertal onset. The ontogenesis of infantile testicular function, including the possible significance of the infantile surge in gonadotropins and testosterone, is reviewed. The molecular basis for certain developmental disorders associated with hypogonadotropic hypogonadism and micropenis is considered and the management and treatment of congenital hypopituitarism discussed.

Adrenocorticotropic Hormone↗
PubMed1985

Single versus repeated dose human chorionic gonadotropin stimulation in the differential diagnosis of hypogonadotropic hypogonadism.

The responses of serum testosterone (T), 17 alpha-hydroxyprogesterone, and 17 beta-estradiol (E2) to four im injections of hCG (5000 IU/1.7 m2) given on days 0, 4, 7, and 10 were studied in 10 prepubertal and 10 pubertal boys with hypogonadotropic hypogonadism (groups O and P, respectively). Serum was obtained before each injection and on day 14. The results were compared with those of controls, 16 prepubertal boys with incomplete testicular descent and 6 pubertal boys with constitutional delay of puberty. Serum T levels increased significantly in groups O and P to 2.0 and 4.6 nmol/liter, respectively, after the first injection, then progressively to 5.8 and 11.2 nmol/liter. Basal T levels of group O did not differ from those of the controls, but were subnormal for group P (P less than 0.001). Stimulated T levels were subnormal in both groups (P less than 0.01 and P less than 0.001), but repeated doses increased the difference from the control value only in group P. A difference in E2 response between patients and controls appeared in puberty; only the pubertal control boys had substantial increases in E2 (P less than 0.001). Our results show that the optimal protocol for a diagnostic hCG test in prepubertal boys is a single dose of hCG, with determination of T levels 4 days later. In puberty, if the basal T levels are inconclusive, repeated doses of hCG should be given with determination of both T and E2. These findings also suggest that the full inhibitory effect of E2 on T synthesis results from a pubertal maturation process, possibly induced by endogenous gonadotropins, which cannot be induced by two weeks of hCG stimulation in prepubertal boys or those with hypogonadotropic hypogonadism.

17-alpha-Hydroxyprogesterone↗
PubMed1985

Events surrounding the initiation of puberty with long term subcutaneous pulsatile gonadotropin-releasing hormone in a female patient with Kallman's syndrome.

An 18-yr-old woman with primary amenorrhea, anosmia, and total lack of secondary sexual development was treated for 230 days using sc pulsatile GnRH. GnRH testing with 100 micrograms, sc, initially revealed a peak FSH to LH ratio greater than 1. After 28 days of treatment, this ratio had reversed. A dosage of 20 micrograms/2 h for 200 days resulted in a LH to FSH ratio greater than 2. Widening the interval to 20 micrograms/3 h significantly lowered LH, but not FSH, levels. Increasing the frequency to 20 micrograms/90 min again increased the LH to FSH ratio. Twenty-four-hour testing revealed a sleep-entrained PRL rise both during and after GnRH therapy, but no sleep-entrained rise in LH. Ultrasound monitoring revealed cyclic changes in ovarian diameter at 30- to 60-day intervals that coincided with cyclic increases in LH and estradiol. The uterine fundus doubled in length between days 50 and 110 of treatment. The patient progressed from Tanner pubic hair and breast stage I to stage II during treatment, which was terminated due to an allergic reaction to GnRH. This study provides the first report of hormonal and ultrasound events surrounding puberty induction with GnRH in the female. We conclude widening the interval of GnRH administration can reduce LH levels while maintaining FSH levels, cyclic changes in ovarian diameter, LH, and estradiol occur before menarche, and although pulsatile GnRH provides a fascinating model for the study of puberty in the female, the chronicity of therapy needed and its potential for allergic reaction make this method of inducing puberty suboptimal.

Adolescent↗
PubMed1985

Prolonged pulsatile administration of luteinizing hormone-releasing hormone in prepubertal children: diagnostic and physiologic aspects.

In order to test gonadotropic function 30 prepubertal and 2 early pubertal girls and boys were treated with LH-releasing hormone (LRH) in a pulsatile fashion for 7 days. LRH was administered iv either in a dose of 10 micrograms every 90 min or in a dose of 20 micrograms/1.73 m2 every 96 min. On days 1 and 7, just before as well as at the end of LRH treatment, a LRH test (100 micrograms/m2 iv) was performed. In 27 patients a LRH test was repeated 4 (day 11) or 7 days (day 14) after LRH withdrawal as well. Plasma LH, FSH, and estradiol or testosterone levels were estimated during the LRH tests on days 1, 7, and 11/14. The patients were divided into 4 groups: group 1 consisted of 2 girls and 1 boy with gonadal failure, group 2 of 1 girl and 2 boys with intact pituitary and gonadal function, group 3 of 11 girls and 13 boys with various central endocrine disorders, and group 4 of 1 girl and 1 boy with pubertal arrest of unknown origin. In group 1 LRH treatment elicited an increase of both gonadotropins into the castrate range, whereas gonadal steroids did not increase. In group 2 baseline LH as well as the response to LRH increased on day 7. In the boys FSH changed similarly. In the girl baseline FSH increased, but the high FSH response of day 1 decreased. Estradiol and testosterone levels were elevated on day 7. These changes during LRH treatment are similar to those during normal pubertal development. When the LRH test was repeated on day 11/14 basal levels had returned into the prepubertal range and a high response of LH especially was found in all 3 subjects. Patients of group 3 were separated into two subgroups: group 3a, those with, and group 3b, those without an increase of gonadal steroids on day 7 of LRH treatment. Since an increment must be the result of increased gonadotropin stimulation, this probably indicates intact gonadotropic function. Group 3a had a pattern of gonadotropin secretion similar to group 2. In group 3b basal and peak LH levels were lower on day 7 compared to group 3a, whereas FSH levels did not differ. Four or 7 days after LRH discontinuation (day 11/14) basal gonadotropin levels were in the original low range. In the LRH test mean LH peak level of group 3a was 43.7 U/liter, of group 3b 13.1 U/liter (P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1987

High serum sex hormone-binding globulin (SHBG) and low serum non-SHBG-bound testosterone in boys with idiopathic hypopituitarism: effect of recombinant human growth hormone treatment.

We measured serum sex hormone-binding globulin (SHBG), total testosterone (T), non-SHBG-bound T, albumin-bound T, free T, and SHBG-bound T in 19 prepubertal boys with hypopituitarism. Serum SHBG decreased with age with a slope similar to that in 91 normal prepubertal boys at higher level, and therefore, it reached similar values at a later age. Serum SHBG was significantly higher in hypopituitary prepubertal boys [mean, 123 +/- 12 (+/- SE) nmol/L] than in normal prepubertal boys (76 +/- 4; P less than 0.001) despite the fact that their mean age was also higher (10.0 +/- 4 vs. 7.1 +/- 4.1 yr; P less than 0.001). In 4 boys with isolated hypogonadotropic hypogonadism (Kallman's syndrome), aged 15.6 +/- 1.5 yr, serum SHBG was 21 +/- 14 nmol/L, a value below the 95% confidence limit of the regression line in GH-deficient boys. The affinity constants of association of the SHBG-DHT complex were similar in hypopituitary and normal boys. Eleven of the 19 hypopituitary boys (mean chronological age, 8.3 +/- 2.5 yr; mean bone age, 4.1 +/- 2.1 yr) were treated with recombinant hGH (0.5 U/kg BW.week) for 1 yr. Their mean serum SHBG level before treatment was 154 +/- 14 nmol/L, and it decreased gradually to 106 +/- 5 nmol/L (P less than 0.01) after 12 months of treatment. The tendency toward normalization of serum SHBG during treatment suggested that GH deficiency was responsible for the high serum SHBG levels. Serum SHBG correlated negatively with age in both treated hypopituitary and normal boys, but the slope of the regression line was significantly steeper in treated hypopituitary boys (P less than 0.01). On the other hand, the mean serum non-SHBG-bound T level was 0.10 +/- 0.02 (+/- SE) nmol/L in hypopituitary boys, significantly lower than that in normal boys (0.21 +/- 0.02 nmol/L; P less than 0.02). Since serum total T concentrations were similar in the two groups, the higher serum SHBG concentration resulted in lower serum bioavailable T levels in the hypopituitary boys. These changes might explain the poor response to T treatment reported in GH-deficient patients. The lower serum non-SHBG-bound T concentrations in the GH-deficient boys suggest there may be delayed exposure of central nervous system structures to increased levels of sex hormones, which, in turn, may slow body maturation. This mechanism might play a role in the delay of puberty that occurs in patients with isolated GH deficiency.

Adolescent↗
PubMed1988

Effects of endogenous sex steroids on serum lipoproteins and postheparin plasma lipolytic enzymes.

Sex steroids influence serum high density cholesterol (HDL) concentrations through their effects on postheparin plasma hepatic lipase activity. This enzyme is remarkably sex steroid sensitive; its activity is increased by treatment with androgens and androgenic progestins but decreased by estrogens. Hepatic lipase also is regulated by endogenous estradiol, but less is known about its regulation by endogenous androgens. We measured serum lipoproteins and postheparin plasma hepatic lipase and lipoprotein lipase activities in relation to sex steroids in 13 boys in whom testicular sex steroid production was stimulated by 4 injections of hCG given at 3-day intervals. Serum testosterone, but not estradiol, concentrations increased in 8 boys (group I, prepubertal and early pubertal boys), whereas in 5 boys both testosterone and estrogen concentrations increased concomitantly (group II, pubertal boys). Postheparin plasma hepatic lipase activity increased by 34% (P less than 0.001) in group I, but did not change in group II. Serum HDL cholesterol concentrations did not change during hCG stimulation. However, postheparin plasma hepatic lipase activity correlated inversely with serum HDL (r = -0.34; P less than 0.05) and HDL2 cholesterol levels (r = -0.51; P less than 0.001), and the changes in HDL2 levels and hepatic lipase activity were inversely related (r = -0.63; P less than 0.05). Postheparin plasma lipoprotein lipase activity decreased during hCG stimulation. Its activity was positively related to HDL (r = 0.47; P less than 0.05) and HDL2 cholesterol levels (r = 0.54; P less than 0.001). These results suggest that endogenous androgens and estrogens are involved in the regulation of postheparin plasma lipase activities and serum HDL cholesterol concentrations.

Adolescent↗
PubMed1989

Testosterone infusion reduces nocturnal luteinizing hormone pulse frequency in pubertal boys.

Administration of testosterone (T) can inhibit LH secretion in early pubertal boys. However, the GnRH pulse generator is relatively resistant to the effects of T, since T infusion beginning at 2100 h, 3 h before the usual nighttime increase in T, does not suppress the characteristic increase in LH pulse frequency or amplitude associated with the onset of sleep in early pubertal boys. To test the hypothesis that the hypothalamic-pituitary axis must be exposed to T for a longer duration to suppress the nocturnal rise in LH pulse frequency and amplitude, we infused saline or T at one third the adult male production rate (320 nmol/h), beginning at 1200 h on two consecutive weekends in each of eight early to midpubertal boys. Blood was obtained from 2000-0800 h every 10 min for LH and every 30 min for T measurements. T infusion increased the mean plasma T concentration from 6.9 +/- 1.7 to 11.8 +/- 1.4 nmol/L (P less than 0.01) between 2000-0800 h. Despite the T infusion, the nocturnal rise in mean LH concentration and LH pulse frequency persisted, suggesting that the nocturnal amplification of LH, and by inference GnRH, secretion is resistant to the negative feedback effects of T. A higher dose of T, approximating the adult male production rate (960 nmol/h), was given to eight additional boys beginning at 1200 h. The mean T concentration increased from 4.2 +/- 1.7 to 20.8 +/- 3.1 (P less than 0.001) nmol/L between 2000-0800 h. The mean plasma LH concentration was suppressed by T infusion from 5.2 +/- 0.5 to 2.9 +/- 0.4 IU/L, and LH pulse frequency decreased from 0.50 +/- 0.04 to 0.27 +/- 0.11 pulses/boy/h (P less than 0.01). There was no nocturnal amplification of LH secretion, but high amplitude LH pulses did occur during the night in six of the eight boys. The low dose T infusion had no effect on pituitary LH release by exogenous GnRH. With the high dose T infusion, however, the ability of GnRH, at 25 ng/kg but not at 250 ng/kg, to release pituitary LH was amplified. Thus, T supplementation at one third the adult male production rate does not blunt the sleep-associated nighttime rise in LH pulse frequency or LH concentration. T infusion approximating the adult male production rate suppresses the nocturnal increase in LH pulse frequency and mean LH concentration, and high amplitude, slow frequency LH pulses similar to patterns seen in adult men persist.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1990

Patterns of pulsatile luteinizing hormone secretion before and during the onset of puberty in boys: a study using an immunoradiometric assay.

To study spontaneous pulsatile LHRH/LH secretion around the onset of puberty, nocturnal plasma LH was measured by means of a highly sensitive immunoradiometric assay in 30 boys (aged 5.6-16.8 yr) investigated for potential problems with growth and/or development. Blood was withdrawn at 10- to 20-min intervals from 2000-0800 h. Pulse analysis was accomplished by a computerized peak detection algorithm. Pituitary and gonadal responsiveness was assessed by a standard exogenous LHRH challenge and testosterone. Subsequent clinical progress was monitored for a mean duration of 2.08 +/- 0.16 yr and used as the basis for classifying patients retrospectively into three groups: 1) prepubertal (n = 14), 2) peripubertal (n = 11), and 3) pubertal (n = 5). LH pulses were undetectable in 9 and present in 5 prepubertal subjects, the youngest of whom was aged 7.3 yr. In peripubertal and pubertal individuals, 2-7 LH pulses/12 h were detectable. LH pulses were detectable before sleep by midpuberty (Tanner stage 3). There was a highly significant (P less than 0.0001) increase in LH/LHRH pulse frequency from 0.93 +/- 0.38 to 4.55 +/- 0.43/12 h (mean +/- SEM) between the prepubertal and peripubertal groups and a further increase to 6.20 +/- 0.37/12 h in the pubertal group. LH pulse amplitude remained under 1.0 U/L in both the prepubertal and peripubertal groups and only increased significantly to 2.02 +/- 0.17 U/L in pubertal boys. Response to LHRH increased significantly between the prepubertal (2.47 +/- 0.49 U/L) and peripubertal (6.53 +/- 2.02 U/L) patients. T increased significantly at each stage, with the greatest rise between the peripubertal and pubertal stages.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Puberty: when?

Explore the source record for details and available documents.

Adolescent↗
PubMed1993

Androgen receptor blockade with flutamide enhances growth hormone secretion in late pubertal males: evidence for independent actions of estrogen and androgen.

Exogenous and endogenous sex steroid hormones influence GH secretion. To test the relative importance of androgens in the enhancement of GH secretion, we administered flutamide (a potent androgen receptor blocker) to six late pubertal males. Blood samples for GH (and LH) were obtained at 10-min intervals for 24-h periods after 3 days of flutamide and during the untreated state. Waveform-specific, multiple-parameter deconvolution analysis was employed to assess secretory and elimination dynamics for GH. Androgen receptor blockade was confirmed by significant increases in 24-h mean LH concentrations and in total 17 beta-estradiol and free testosterone levels in the serum. Mean serum GH concentrations (24-h) also increased (P < 0.001) during androgen receptor blockade (mean +/- SEM, 2.9 +/- 0.3 vs. 1.8 +/- 0.3 micrograms/L); this was associated with an increased (P < 0.001) GH production rate [152 +/- 15 vs. 93 +/- 16 micrograms/liter of distribution volume (Lv)/24 h]. The enhanced GH secretion during flutamide administration was a result of both increased mass of GH released per secretory burst (12.0 +/- 1.4 vs. 8.4 +/- 1.0 micrograms/Lv; P < 0.005) and increased maximal rate of GH secretion (0.39 +/- 0.04 vs. 0.30 +/- 0.03 micrograms/Lv/min; P < 0.05), as well as a small increase in the number of detectable secretory bursts (12 +/- 1 vs. 10 +/- 1/24 h; P < 0.05). There was no significant change in either the serum half-life of GH or in the half-duration of GH secretory bursts during androgen receptor blockade. We speculate that the augmentation of GH secretion observed during antagonism of androgen action in late pubertal males is a result of increased stimulation of estrogen receptor-mediated pathways. Alternatively, androgens may exert a tonic inhibition of GH secretion which can be abolished by androgen receptor blockade.

Adolescent↗
PubMed1994

Usefulness of sequential urinary follicle-stimulating hormone and luteinizing hormone measurements in the diagnosis of adolescent hypogonadotropism in males.

FSH and/or LH deficiency in the second decade of life remains difficult to diagnose with testing at a single point in time because of the partial lack of hormone as well as the dynamic and inherently variable aspects of the pubertal process. A longitudinal study of gonadotropin excretion, therefore, was carried out in 78 normal boys and 157 male patients, aged 10-28 yr, with relative or absolute deficiencies of FSH and/or LH. Seven hundred and fifty-five timed urine samples were extracted with acetone, concentrated, and subjected to RIA. The results from patient groups with multiple tropic hormone deficiencies or isolated gonadotropin deficiency were clearly different from those of normal boys and individuals with constitutional delay in puberty. However, multiple samples obtained over a 2-yr period and, in selected cases, until the late teenage years may be required to diagnose gonadotropin deficiency in some patients, even using stringent predictive modeling criteria.

Adolescent↗
PubMed1998

Exaggerated free alpha-subunit levels during pulsatile gonadotropin-releasing hormone replacement in women with idiopathic hypogonadotropic hypogonadism.

The goals of this study were to determine whether women with idiopathic hypogonadotropic hypogonadism (IHH) respond to pulsatile GnRH replacement therapy with exaggerated glycoprotein free alpha-subunit (FAS) levels, as reported in GnRH-deficient men, and to determine whether this pattern is unique to congenital GnRH deficiency or is also characteristic of patients with hypogonadotropic hypogonadism caused by other factors. GnRH was administered i.v. at a physiologic frequency and dose (75-100 ng/kg.bolus) to women with IHH (n = 11; n = 6 with anosmia); acquired GnRH deficiency secondary to treatment for cranial tumors (AHH; n = 7); and secondary hypothalamic amenorrhea (HA; n = 8). Results were compared with 24 normal cycling women. Gonadotropins, sex steroids, and FAS levels were measured in samples drawn daily across induced or normal menstrual cycles in patients or normal women, respectively. Samples were drawn at the same time of day and were collected 45 min after a GnRH bolus in patients. All women ovulated in response to pulsatile GnRH. There were no differences in the patterns of LH or gonadal steroid secretion between any of the patient groups (IHH, AHH, and HA). The patterns of LH and FSH secretion in the induced patient cycles were not different from normal women, with the exception of lower midcycle FSH levels in IHH women (P < 0.002). However, the daily dynamic secretion of FAS was exaggerated in IHH (compared with AHH, HA, and normal) women (P < 0.002). The increase in FAS levels in IHH was dependent on cycle stage, with the greatest difference observed during the early (P < 0.005) and midfollicular phase (P < 0.05) and the early luteal phase (P < 0.05). There was no difference in FAS between groups during the late follicular phase, at the midcycle, or in the midluteal and late luteal phase. This exaggerated FAS response to GnRH replacement in IHH was demonstrated in repeat cycles in two patients. Conclusions are: 1) Women with IHH respond to pulsatile GnRH replacement with an exaggerated secretion of FAS, which seems to be modified by gonadal factors; 2) this exaggerated FAS response, which is similar to that seen in GnRH-deficient men, is unique to congenital GnRH deficiency, and it is not observed in patients with acquired or secondary hypogonadotropic hypogonadism, suggesting that IHH patients may be missing a factor, in addition to GnRH, which normally restrains FAS secretion; and 3) the FAS response may prove to be a useful marker to distinguish constitutional delay of puberty from congenital GnRH deficiency.

Adolescent↗
PubMed1998

A homozygous mutation in the luteinizing hormone receptor causes partial Leydig cell hypoplasia: correlation between receptor activity and phenotype.

Leydig cell hypoplasia (LCH) is characterized by a decreased response of the Leydig cells to LH. As a result, patients with this syndrome display aberrant male development ranging from complete pseudohermaphroditism to males with micropenis but with otherwise normal sex characteristics. We have evaluated three brothers with a mild form of LCH. Analysis of their LH receptor (LHR) gene revealed a homozygous missense mutation resulting in a substitution of a lysine residue for a isoleucine residue at position 625 of the receptor. In vitro analysis of this mutant LHR, LHR(I625K), in HEK293 cells indicated that the signaling efficiency was significantly impaired, which explains the partial phenotype. We have compared this mutant LHR to two other mutant LHRs, LHR(A593P) and LHR(S616Y), identified in a complete and partial LCH patient, respectively. Although the ligand-binding affinity for all three mutant receptors was normal, the hormonal response of LHR(A593P) was completely absent and that of LHR(S616Y) and LHR(I625K) was severely impaired. Low cell surface expression explained the reduced response of LHR(S616Y), while for LHR(I625K) this diminished response was due to a combination of low cell surface expression and decreased coupling efficiency. For LHR(A593P), the absence of a reduced response resulted from both poor cell surface expression and a complete deficiency in coupling. Our experiments further show a clear correlation between the severity of the clinical phenotype of patients and overall receptor signal capacity, which is a combination of cell surface expression and coupling efficiency.

Adult↗
PubMed1988

Menarche in athletes: the influence of genetics and prepubertal training.

It is unclear whether the later menarche observed in competitive athletes is due to genetic factors or environmental factors related to intense prepubertal training. In order to investigate the importance of these factors upon the age of menarche (AOM), 263 competitive swimmers and 71 women with no athletic experience were asked to complete questionnaires concerning general health and reproductive development. Based upon their responses, similar questionnaires were sent to the sisters of both groups. Complete data were obtained from 140 athlete/sister pairs and 43 control/sister pairs. Results indicate that the athletes were older at menarche than their sisters, the non-athletes, and the sisters of the non-athletes (14.3 yr, 13.7 yr, 12.9 yr, and 13.0 yr, respectively). The sisters of the athletes were significantly older at menarche than the controls and their sisters, while the AOM of the non-athletic controls and their sisters did not differ. The interpretation of the data is complicated by the fact that the sisters of the athletes were likely to be athletes (75%), while those of the control group tended to be non-athletic (74%). The athletes differed from their sisters who trained prior to menarche (13.9 years) and from those who did not engage in prepubertal training (13.1 years). Controls did not differ from any of their sister groups, nor did they differ from the untrained sisters of athletes. In terms of the similarity of the AOM within the sister pairs, the athletes/sisters and controls/sisters were equally similar. Significant correlations were observed between athletes and their sisters who trained prior to menarche and controls and their sisters who did not.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Growth at puberty: interaction of androgens and growth hormone.

Puberty is characterized by the onset and continued development of secondary sexual characteristics and an abrupt onset of linear growth. Growth in boys occurs due to the rising levels of androgens and also indirectly mediated by growth hormone (GH) and the insulin-like growth factors. Data are presented to show marked androgen-dependence of GH increases at puberty. The mode of this increase is through an augmentation in the amplitude of the pulses rather than in their frequency. Shortly after the maximal rate of growth, the pattern of GH release reverts toward that of the prepubertal child. To investigate the neuroendocrine mechanism through which androgens increase the mean circulating GH level, deconvolutional analysis has been applied. At mid-puberty the maximal rate of GH release per secretory burst and the total amount released per burst were increased. There were no significant alterations in the duration or frequency of the GH secretory burst or in the serum half-life reflecting the metabolic clearance of the hormone. Thus, the pubertal growth spurt in boys is likely subserved by the altered neurosecretory dynamics for GH. These altered hormone levels likely produce the equally profound changes in body composition, regional fat distribution, and muscular strength that occur during puberty in boys.

Adolescent↗