Serum relaxin‐3 hormone relationship to male delayed puberty

Puberty is the transitional period between childhood and adulthood, a process encompassing morphological, physiological and behavioural development to attain full reproductive capability. This study aimed to assess serum relaxin‐3 hormone relationship with male delayed puberty. Sixty males were investigated as two equal groups: males with delayed puberty and healthy matched males as controls. They were subjected to history taking, clinical examination and estimation of serum FSH, LH, testosterone, relaxin‐3 hormonal levels. The results showed that the secondary sexual characters in the patients group were at Tanner stages 1–2 and in the healthy controls at Tanner stages 3–5. The mean BMI in the patients group was significantly increased, whereas the mean levels of the span, testicular volume, serum LH, FSH, testosterone as well as relaxin‐3 hormonal levels were significantly decreased compared with the healthy controls. Serum relaxin‐3 levels showed significant positive correlation with the age, testis volume, span, Tanner stages, serum testosterone, FSH, LH hormones. In addition, serum relaxin‐3 levels showed significant negative correlation with BMI. It is concluded that serum level of relaxin‐3 hormone is an important mediator in the pathophysiological process of normal puberty being significantly decreased in males with delayed puberty.     

Temporal relation between leptin and various indices of sexual maturation in the male rat.

Recent studies in humans and rhesus monkeys have suggested the possibility that the adipose tissue hormone leptin has a stimulatory and/or permissive effect on the onset of puberty in the male. We evaluated this hypothesis by measuring leptin in groups of male rats between the ages of 26 days and 96 days. A statistically significant positive correlation was present between serum leptin and age, body weight, prostate, seminal vesicle, and testes weight (both absolute and as a function of body weight). A statistically significant negative correlation was present between leptin and serum FSH and alpha-inhibin. There was not a statistically significant correlation between leptin and testosterone or LH. There was a statistically significant increase in the serum leptin concentrations at day 47. This rise was coincident with the peripubertal growth spurt in the secondary sexual organs and the peripubertal testosterone rise but occurred after the prepubertal rise in testicular weight, the appearance of elongating spermatids in the testes, and the start of the decline in FSH. In animals in which the peripubertal testosterone rise was delayed by the administration of EDS, serum leptin showed statistically significant differences from control. These data do not support the hypothesis that leptin provides a trigger for the onset of puberty in the male rat. They do suggest that leptin may be involved in the secondary sexual organ growth spurt and are consistent with the hypothesis that testosterone stimulates leptin synthesis during puberty.     

Pre- and postnatal testosterone administration induces proliferative epithelial lesions with neuroendocrine differentiation in the dorsal lobe of the rat prostate.

BACKGROUND: Androgens are implicated in the pathogenesis of prostatic carcinoma. We have elucidated the role of pre- and postnatal testosterone administration in the occurrence of proliferative lesions as well as neuroendocrine (NE) cells in the rat prostatic complex. METHODS: Female rats were given a single dose of 9 mg testosterone enantate i.m. on day 15 of pregnancy; it gave a high testosterone exposure to the fetus in the early organogenetic period of the rat prostatic complex. One group of the male offspring was followed without further testosterone treatment; a second group received testosterone only in the pubertal period; a third group was given testosterone from puberty and throughout life (46 weeks). These groups were compared to parallel groups (1A-1C) of male offspring without a testosterone supplement in pregnancy. RESULTS: The serum testosterone concentrations in the rats receiving testosterone were significantly higher than those of control rats. Histopathologically, the testosterone-induced proliferative lesions, mainly hyperplastic, were almost exclusively located in the dorsal lobe. Chromogranin A-immunoreactive (CgA-IR) cells were rarely found normally, but occurred more often in the proliferative lesions (P < 0.001). CONCLUSIONS: The incidence of proliferative lesions in rats exposed to testosterone only in puberty was comparable to the incidence found in those rats receiving testosterone in puberty and throughout life. This finding may have clinical implications for young athletes, who use testosterone as an anabolic drug. The occurrence of CgA-IR cells increased in proliferative lesions in the dorsal lobe of the rat prostatic complex.     

Testosterone concentrations in human seminal plasma and saliva and its correlation with non-protein-bound and total testosterone levels in serum

A sensitive, specific and precise non-chromatographic method for the radio-immunoassay of testosterone in human seminal plasma and saliva from adult and pubertal males is described, and the values compared to total and non-protein-bound testosterone levels in serum. There was a significant correlation between salivary and serum-free levels of testosterone (r = 0.75, P < 0.001, n = 67) whilst the correlation of serum levels of total testosterone with free as well as with salivary testosterone levels was weaker (r = 0.63 and 0.64, respectively). The salivary and serum levels of free testosterone showed better correlation with the stage of puberty than did the serum levels of total testosterone. Further evidence for a correlation between salivary and serum levels of free testosterone was obtained following oral administration of testosterone undecanoate, as this treatment increased the mean concentration of serum total testosterone after 3 h by 82%, but increased salivary and serum levels of free testosterone by only 30% and 20%, respectively. The coefficient of correlation between serum levels of total testosterone and seminal plasma testosterone was 0.73 ( P < 0.001), whilst the correlation between levels of serum-free testosterone with both salivary and seminal plasma levels of testosterone was statistically non-significant. Our observations on salivary testosterone are in accordance with the diffusion of non-protein-bound steroids into peripheral tissues, and consequently into their secretions. This model, however, does not appear to be applicable to the sex accessory glands.     

Isoflavones and their effects on the onset of puberty in male Wistar rats

This study was performed to determine how two of the most important isoflavones, genistein and daidzein, affect the gonadal axis in male prepuberal rats. One hundred and seventy‐five prepuberal male Wistar rats were allocated into seven groups: one control group and six experimental groups that were orally administered a high or low dose of genistein, daidzein or a mixture of both. Testosterone determination was assayed by EIA. The testes and body weights were measured, and the histology of the epididymis with the sperm content and epididymal sperm count were evaluated. In the control group, we observed an increase in the serum testosterone levels (>2.5 ng ml^?1) at the third week (52 days), which corresponded to the onset of puberty in these rats. The same increase in serum testosterone levels was observed at the fourth week in rats that received low doses of isoflavones; therefore, we concluded that the onset of puberty was delayed. At high doses, there was no significant increase in testosterone levels, which could be related to the fact that these male rats did not reach puberty. These findings were supported by the results obtained from the analysis of the epididymal content as well as the testes/body weight ratio.     

Bone turnover in male puberty: A longitudinal study

Summary In a longitudinal study of male puberty, 18 boys were examined every 3 months for at least 2 years. Serum bone Gla protein (BGP), a biochemical marker of bone formation, was determined and related to changes in serum testosterone (T), serum alkaline phosphatase (AP), serum calcitonin, and bone mineral content (BMC). The data demonstrate a steep increase in serum T during puberty (P<0.001), with an almost concomitant increase in serum BGP (P<0.001) and serum AP (P<0.001). Ten months after the maximal increase in serum T, the increase in BMC reached its maximum, whereas there was no significant change in the serum calcitonin. The data demonstrate that the steep increase in serum T during puberty, directly or indirectly, produces acute stimulation of bone formation (estimated from BGP and AP) followed by a highly significant increase in the integrated measurement of bone apposition (BMC).     

唾液游离睾酮测定的临床应用

借鉴国内外文献报告的方法，建立了唾液游离睾酮的测定方法，可替代血游离睾酮的测定。本法批内变异系数５．７５％，批间变异系数８．４５％，提取回收率９４％，最小检出量（灵敏度）１２．３０ｐｇ（９５％可信限）。唾液游离睾酮与血清总睾酮之间有极好的相关性（ｒ＝０．９８４，Ｐ＜０．００１）。唾液游离睾酮测定方法实用、可靠，在临床应用中取得满意结果，加之取材容易，病人易于接受，具有很好的社会和经济效益。     

Diagnosis and therapy of hypogonadism in adult males

Hypogonadism in men is defined as endocrine dysfunction of the testes, and due to reduced serum testosterone levels leads to symptoms of testosterone deficiency. Depending on the location of disruption in the endocrinological cycle, hypogonadism is classified as primary, secondary, or tertiary. In primary hypogonadism, the production of testosterone in the Leydig's cells of the testes does not function properly. Serum LH concentrations are elevated in the sense of counterregulation (hypogonadotropic hypogonadism). In secondary hypogonadism, LH secretion (and usually also FSH) from the hypophysis is impaired so that Leydig's cells are not stimulated, while in tertiary hypogonadism the hypothalamus is damaged. The clinical course in cases of reduced serum testosterone levels is determined essentially by the point in time when hypogonadism becomes manifest. Delayed puberty, eunuchoid stature, and underdeveloped secondary sex characteristics suggest prepubertal onset of hypogonadism.     

Enucleation for prepubertal leydig cell tumor

PURPOSE: Leydig cell tumors in children are rare, comprising only 4% to 9% of all primary testis tumors in prepubertal males. Almost all of these boys present with isosexual precocious pseudopuberty associated with increased testosterone, low gonadotropin levels and a testis mass. We present our experience with testis sparing enucleation of Leydig cell tumor in prepubertal boys. MATERIALS AND METHODS: Two patients presented with isosexual precocious puberty at ages 6 and 9 years. Each patient had a well circumscribed, painless testicular mass, increased serum testosterone (101 and 444 ng/dl [normal 0 to 25]), normal gonadotropins and negative alpha-fetoprotein levels. Both patients underwent successful enucleation of the testis mass following proper testis oncological surgical principles. RESULTS: Both patients had normalization of the serum testosterone following enucleation of the Leydig cell tumor. At 9 and 44 months of followup they have maintained normal ipsilateral testicular volume compared to the contralateral gonad, and 1 patient entered puberty spontaneously at 1 year postoperatively. Neither patient suffered any morbidity, and both have presumably benefited from preservation of the involved gonad with preserved testicular volume. CONCLUSIONS: Prepubertal boys with isosexual precocious pseudopuberty, an isolated testis mass, increased testosterone and low or normal gonadotropin levels can reliably be diagnosed with Leydig cell tumors. Based on the ability to establish the diagnosis preoperatively and the universal benign behavior of unilateral, prepubertal Leydig cell tumor, we believe these patients are best treated with testis sparing enucleation of the tumor. In view of the high likelihood that this tumor in prepubertal boys is benign, a transscrotal surgical approach should be considered.     

Hypothalamic hamartoma with precocious puberty--a case report

A case of hypothalamic hamartoma with precocious puberty is presented and the literature of reported cases is reviewed. An 8-year-old boy was admitted to our hospital because of precocious puberty and mental retardation. His genital development was Tanner's stage 4 and pubic hair was Tanner's stage 3. Bone age was 11 years. Plain CT showed an isodense mass in the suprasellar cistern which was not enhanced following contrast administration. Metrizamide CT cisternography showed a filling defect in the suprasellar cistern. Endocrinological evaluation revealed high levels of serum luteinizing hormone (LH) and testosterone with a marked response of LH to LH-RH injection. A left frontotemporal craniotomy was performed and the tumor was partially removed. The tumor was gray, firm and well-circumscribed with poor vascularity. Postoperatively, a right oculomotor palsy and transient diabetes insipidus developed. He was discharged ambulatory one month later. Serum LH and testosterone returned to normal and the response of LH to LH-RH injection became normal. Hamartoma was diagnosed on histological examination. Electron micrographic study showed numerous dense granules with approximately 0.1 mu in diameter, in which Judge proved LH-RH by immunofluorescent study in 1977. Our case supports the hypothesis that hypothalamic hamartoma may cause precocious puberty by autonomous secretion of LH-RH and we consider that neurosurgical treatment is recommended.     

Three cases of Klinefelter syndrome in childhood--endocrinological and gonadal changes in puberty

Three children at the ages of 4, 10 and 12 years, with external genital malformation, were diagnosed to be with the Klinefelter syndrome by chromosome analysis. To clarify the pubertal changes in this syndrome, all of them were studied for physical and endocrinological examinations and two underwent testicular biopsy. Before puberty any remarkable abnormality were not observed in the hypothalamus-pituitary-gonadal axis and in the physical status. After the onset of puberty they started showing increases of the basal levels of plasma FSH and LH with over-response to LH-RH stimulation test. During the period of this study the levels of plasma testosterone were in the normal range and increased gradually with age. One boy showed a transient high level of plasma testosterone at early puberty. The reactions of plasma testosterone to HCG stimulation of all cases showed the normal pattern. The histological examination of the testis revealed that the number of spermatogonia was reduced in both cases compared with that of normal boys reported by Mancini et al. These findings indicate that most endocrinological and histological abnormalities in adult Klinefelter syndrome occur after the onset of puberty. These changes may be induced at puberty by hypergonadotrophic condition which result from slightly impaired testicular function which is present before puberty.     

The influence of serum ghrelin,IGF axis and testosterone on bone mineral density in boys at different stages of sexual maturity

The aim of our study was to examine the relationship between bone mineral density (BMD) and serum ghrelin, insulin-like growth factor-1 (IGF-1), IGF-binding protein 3 (IGFBP-3), and testosterone levels in boys at different stages of puberty. The study included 60 healthy nonobese Estonian schoolboys at the age of 10–18 years. Subjects were divided in three groups (20 boys in each) based on the results of self-assessment using illustrated questionnaire of pubertal stage (G1, I; G2–G3, II; G3–G4, III). Morning fasting blood samples were collected for analysis of ghrelin, testosterone, IGF-1, and IGFBP-3. Total body BMD, lumbar BMD, lumbar apparent volumetric BMD (BMAD), and bone mineral content (BMC) were measured by DXA. Serum testosterone concentration was the most important biochemical predictor of BMD in the total group, explaining 48.8% of variability in total body BMD, 51.4% in lumbar BMD, and 36.8% in lumbar BMAD. Body mass and height were both related to BMD and BMC throughout puberty. The serum IGF-1/IGFBP-3 ratio was correlated with serum testosterone (r = 0.69) and ghrelin (r = −0.58) levels, but also with total BMD (r = 0.39), lumbar BMD (r = 0.42; P < 0.001 in all cases), BMAD (r = 0.29; P < 0.01), and total BMC (r = 0.48; P < 0.001). We conclude that serum testosterone concentration and serum IGF-1/IGFBP-3 molar ratio are the major determinants of bone mineral density in boys at different pubertal stages. Serum ghrelin concentration did not appear to have a direct independent effect on BMD. If present, the association may be mediated through sex hormones and the GH-IGF-I axis.     

Leptin secretion from the epididymal fat pad is increased by the sexual maturation of the male rat

Although leptin has been implicated as an important factor in triggering the onset of puberty in females, much less is known about the role of this adipose tissue hormone in the sexual maturation of males. Previous work in the rat has suggested that the peripubertal rise in testosterone precedes an increase in leptin secretion, and it has been suggested that the testosterone rise induces the leptin increase. These studies examined some of the interactions between leptin secretion and the peripubertal testosterone rise in male rats. Serum leptin concentrations were significantly elevated in young adult male rats compared with immature rats. Cultured epididymal fat pads obtained from adult animals secreted significantly more leptin than did those obtained from immature rats. Castration of immature rats with or without testosterone replacement for 1 week did not result in a significant change in either the serum leptin concentrations or the ability of the epididymal fat pad to secrete leptin. Exposure of epididymal fat to 5 ng/mL of testosterone in vitro resulted in a significantly enhanced secretion of leptin into the media compared with plain media controls. These results confirmed that there is an increase in serum leptin concentrations with sexual maturation in the male rat. They also suggest that this increase is due to an enhanced ability of adipose tissue to secrete leptin. Within a normal physiologic range, testosterone may play a role in inducing this increased ability to secrete leptin.     

Plasma testosterone and estradiol levels in unilateral cryptorchidism

This research was conducted to investigate the relationship between plasma hormone level during activation of hypothalamic-pituitary-testicular axis at the postnatal period and at puberty in unilateral cryptorchidism. Plasma testosterone and estradiol levels of 80 patients with unilateral cryptorchidism at different ages (range: 6 months-12 years) were measured. The mean plasma testosterone level is 40 (15-60) pg/ml at 6 months of age, 55 (30-120) at ages between 9 and 12 years, and 20 (11-22) at ages between 1 and 9 years. The mean plasma estradiol level is 12, 11 and 11 (5-24) pg/ml, respectively, in these groups. The patients with unilateral cryptorchidism do not have similar peaks of plasma estradiol level as plasma testosterone level at the postnatal period and at puberty. Peak of plasma testosterone at puberty occurs if the patients were not operated on.     

青春期小阴茎的规范性诊疗

目的观察12~16岁患儿小阴茎发育情况,探讨青春期小阴茎治疗效果。方法回顾性分析2017年8月至2019年4月治疗的28例青春期小阴茎患儿,其中睾酮治疗组21例,睾酮联合来曲唑治疗组7例,观察睾酮组与联合组患儿阴茎牵拉长度(SPL)。结果睾酮组治疗前SPL(4.1±0.9)cm,用药后3个月SPL(6.7±0.6)cm;联合组患儿治疗前SPL(4.3±0.9)cm,用药后3个月SPL(7.4±1.0)cm,两组患儿用药后3个月SPL较治疗前明显增长(P<0.01),效果显著。结论青春期小阴茎患儿早期给予睾酮或联合来曲唑治疗,阴茎增长效果满意。青春期小阴茎患儿应该足够重视,早期发现,积极明确原因,补充睾酮治疗,必要时联合来曲唑,促进阴茎发育。     

A case of Kallmann syndrome: usefulness of the aging male's symptoms rating scale for assessment of subjective symptoms

We report a case of Kallmann syndrome in which the aging male's symptoms rating scale (AMS) was useful for assessment of subjective symptoms. A 30-year-old male was admitted to Tsukuba University Hospital with a complaint of delayed puberty in May 2003. He presented with hypogonadism, gynecomastia and anosmia. The plasma levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone were very low. However, the LH-releasing hormone test and human chorionic gonadotropin (hCG) loading test identified normal function of pituitary and Leydig cell. After 12 months of treatment with hCG and human menopausal gonadotropin (hMG), the amount of pubic hair and the volume of testes had increased as well as the level of serum testosterone. The total score of AMS after treatment has been improved from 39 to 20 as compared with that before treatment.     

Effects of induced hypoprolactinemia on testicular function during gonadal maturation in the rat

We have evaluated the effects of hypoprolactinemia during gonadal maturation in the male rat. Intact 30-day-old rats were injected daily for 10 days with three different doses of bromocriptine (0.75, 1.5 or 3.0 mg/kg of body weight/day). At the end of the treatment period, the animals were sacrificed, serum was collected for prolactin (PRL), LH, and androgen measurements. Intratesticular testosterone and 5 alpha-androstanediol (androstanediol) were measured following celite column chromatography and a specific radioimmunoassay. In addition, the production of androgens by decapsulated testes and dispersed Leydig cells was also studied in vitro. Serum levels of PRL (9.4 +/- 1.9 ng/ml) were suppressed to undetectable levels in the three bromocriptine-treated groups, whereas LH levels were not altered. All three doses of bromocriptine markedly depressed serum testosterone (plus DHT) and androstanediol. Intra-testicular testosterone and androstanediol were diminished (25% and 35%, respectively, P less than 0.05) during hypoprolactinemia. Decapsulated testes and dispersed Leydig cells from bromocriptine-treated animals showed a significant reduction in the basal secretion of testosterone (plus DHT) and androstanediol, and in androgen responses to submaximal hCG stimulation. Maximal steroidogenic responses from bromocriptine-treated rats were similar to controls. The present findings show that, during puberty, bromocriptine influences testicular steroidogenesis, and these effects may be partly due to changes in PRL levels. A direct effect of this dopaminergic agonist on the male gonad cannot be completely ruled out.     

Effect of prenatal vitamin D (calcitriol) exposure on the growth and development of the prostate.

BACKGROUND: We previously found that in the absence of testosterone (T), calcitriol promotes proliferation of normal prostatic stroma, while in the presence of T, it has a differentiating effect on prostatic epithelium. The present study was conducted to determine the effect of calcitriol exposure in utero on the postnatal development of the normal prostate. METHODS: Pregnant rats were injected subcutaneously with either 1.25 microg of calcitriol or vehicle alone on alternate days till delivery. Calcitriol-exposed and control pups were sacrificed at age 25 days (prepuberty), 63 days (postpuberty), or 102 days (adults), and their prostates and seminal vesicles were harvested and weighed. RESULTS: Pups prenatally exposed to calcitriol and sacrificed before puberty (25 days) had a 35% greater mean prostatic weight than controls (0.0314 vs. 0.0422 g, P < 0.007), and calcitriol-exposed adult rats (102 days) had a 68% greater mean prostatic weight than controls (0.1365 vs. 0.2304 g, P < 0.005). No differences were observed in seminal vesicle weights, and in serum calcium and testosterone levels. A disproportionately high mortality rate from sudden death (71%) was observed at puberty in uncastrated male rats prenatally exposed to calcitriol. CONCLUSIONS: These findings suggest that high-dose calcitriol exposure in utero may uniquely influence subsequent prostatic growth. Nonandrogenic steroids such as calcitriol may also be involved in genetic imprinting of the prostate.     

Endocrine profiles in pediatric andrology. III. Human chorionic gonadotropin stimulation test in cryptorchid boys

Serum testosterone (T) concentration and urinary 17-ketosteroid (17-KS) excretion were measured under basal conditions and after stimulation with human chorionic gonadotropin (hCG) in 36 prepubertal males (10 normal children and 26 cryptorchid patients). As a function of hCG stimulation, the increase in serum T level was evident in both groups, although the magnitude of the rise was higher in the control group than in cryptorchid boys. No significant differences in serum T or urinary 17-KS were observed between patients with unilateral and bilateral undescended testis, either before or after hCG stimulation. In spite of the wide individual variations in testicular response in all subjects, the test is valuable in assessing Leydig-cell function and in prognosis for virilization at puberty.     

Evolution of somatic and germ cell populations after busulfan treatment in utero or neonatal cryptorchidism in the rat

Summary.  In order to elucidate the respective effects of depletion of germ cells and of increase in testicular temperature, rats of the same Wistar strain were rendered experimentally bicryptorchid or sterilized by a busulfan injection in utero and compared to control animals. In both models, germ cells were depleted but numeric evolution and functions of somatic cells differed. The aim of that work was to compare the numeric evolutions of testicular somatic and germ cells to their respective functions in each model before puberty and in adult rats of the same strain. Serum concentrations of FSH, LH and testosterone were compared at 20, 40 and 110 days of age. Histological analyses of Sertoli and germ cells in the seminiferous tubules and of Leydig cells in the intertubular tissue were performed before puberty and at adulthood. Testosterone serum concentrations were depleted in both models starting at 40 days of age and more in busulfan-treated rats. Both FSH and LH levels were increased from 20 days onwards in experimental rats. Additional cryptorchidism in busulfan-treated rats depressed the serum testosterone concentration. At 17 days of age, the cryptorchidism do not modify somatic or germ cell populations while busulfan treatment has induced a decrease of both these populations. Conversely, the cross sectional area of the somatic testicular cells was not affected whatever the treatment. In adult testes of busulfan-treated and cryptorchid rats, the total numbers of Sertoli and Leydig cells and of germ cells per testis were decreased. The cellular size of the perivascular Leydig cells was not modified by any of the treatments whereas the size of the Sertoli cells was reduced.
In conclusion, in both models the absence of germ cells induces a decrease in Sertoli cell function, while the increase in testicular temperature provokes degeneracies of Sertoli and germ cells in the seminiferous tubules of the rat.