Inhibin B levels in adolescents and young adults with type 1 diabetes

OBJECTIVE/METHODS: To assess exocrine and endocrine testicular function in subjects with diabetes, we evaluated serum inhibin B, gonadotrophins and testosterone levels in 33 male adolescent and young adult patients affected by type-1 diabetes (age 21.0 +/- 5 years; range 14.2-33.3), with a mean disease duration of 12.7 +/- 5.8 years (range 1.5-25.3) and various metabolic control (HbA1c 7.8 +/- 1.5%; range 5.5-13.2) and compared them with those of an age-matched group of 36 healthy control subjects (age 19.5 +/- 4.1 years; range 13.6-28.1). Both patients and controls had a testicular volume >or=15 ml. Inhibin B was measured by ELISA method. RESULTS/CONCLUSION: Diabetics and controls had comparable inhibin B (203 +/- 74 vs. 221 +/- 69 pg/ml, respectively) and follicle-stimulating hormone (FSH) levels, while luteinizing hormone (LH) and testosterone levels were significantly higher in the diabetic group. Inhibin B was negatively correlated both in patients and controls with FSH, while a negative correlation with LH was found only in the diabetic group. We conclude that our young diabetic males, after a mean disease duration of 12 years and various metabolic control, had inhibin B and FSH levels comparable to those of normal subjects. Therefore, they seem to have a regular testicular function and in particular a normal seminiferous tubule/Sertoli cell activity despite sustained hyperglycemia.     

McCune-Albright syndrome in a boy may present with a monolateral macroorchidism as an early and isolated clinical manifestation

BACKGROUND: Testis enlargement in McCune-Albright syndrome (MAS) is generally bilateral and associated with clinical and biochemical manifestations of sexual precocity. CASE REPORT: We describe for the first time an unreported clinical expression of MAS in a 4.6-year-old boy presenting with monolateral testis enlargement and no signs of sexual precocity or other clinical manifestations of MAS at the time of presenting with macroorchidism. Both testosterone and LHRH-stimulated gonadotropin levels were in the prepubertal range. Serum inhibin B was increased to a pubertal level indicating Sertoli cell activation. The histological and immunocytochemical evaluation of the enlarged testis revealed Sertoli cell hyperplasia with no mature Leydig cells. Mutation R201C of GNAS1 gene, classically responsible for MAS, was identified in DNA samples from the right testis biopsy and leukocytes. CONCLUSIONS: (a) MAS should be taken into consideration in the clinicopathological approach to a boy with monolateral macroorchidism; (b) testicular enlargement may be only the presenting clinical manifestation of MAS and is not necessarily linked to manifestations of peripheral precocious puberty; (c) testicular autonomous hyperfunction in MAS may be restricted to Sertoli cells, as also demonstrated previously by others.     

An activated human follicle-stimulating hormone (FSH) receptor stimulates FSH-like activity in gonadotropin-deficient transgenic mice

FSH mediates its testicular actions via a specific Sertoli cell G protein-coupled receptor. We created a novel transgenic model to investigate a mutant human FSH receptor (FSHR(+)) containing a single amino acid substitution (Asp567Gly) equivalent to activating mutations in related glycoprotein hormone receptors. To examine the ligand-independent gonadal actions of FSHR(+), the rat androgen-binding protein gene promoter was used to direct FSHR(+) transgene expression to Sertoli cells of gonadotropin-deficient hypogonadal (hpg) mice. Both normal and hpg mouse testes expressed FSHR(+) mRNA. Testis weights of transgenic FSHR(+) hpg mice were increased approximately 2-fold relative to hpg controls (P < 0.02) and contained mature Sertoli cells and postmeiotic germ cells absent in controls, revealing FSHR(+)-initiated autonomous FSH-like testicular activity. Isolated transgenic Sertoli cells had significantly higher basal ( approximately 2-fold) and FSH-stimulated ( approximately 50%) cAMP levels compared with controls, demonstrating constitutive signaling and cell-surface expression of FSHR(+), respectively. Transgenic FSHR(+) also elevated testosterone production in hpg testes, in the absence of circulating LH (or FSH), and it was not expressed functionally on steroidogenic cells, suggesting a paracrine effect mediated by Sertoli cells. The FSHR(+) response was additive with a maximal testosterone dose on hpg testicular development, demonstrating FSHR(+) activity independent of androgen-specific actions. The FSHR(+) response was male specific as ovarian expression of FSHR(+) had no effect on hpg ovary size. These findings reveal transgenic FSHR(+) stimulated a constitutive FSH-like Sertoli cell response in gonadotropin-deficient testes, and pathways that induced LH-independent testicular steroidogenesis. This novel transgenic paradigm provides a unique approach to investigate the in vivo actions of mutated activating gonadotropin receptors.     

Fertility after unilateral cryptorchidism. Paternity, time to conception, pretreatment testicular location and size, hormone and sperm parameters.

OBJECTIVE: To further evaluate whether fertility is decreased among a cohort of men with previous unilateral cryptorchidism as compared with a control group of men. SUBJEcTS AND METHODS: Formerly unilateral cryptorchid men who had undergone orchiopexy between the years of 1955 and 1975 at the Children's Hospital of Pittsburgh and a control group of men who were matched for age of an unrelated surgery at the same institution were evaluated by review of medical records and by completion of a questionnaire. 359 previously cryptorchid men were identified as having attempted paternity. Of these men, 320 had information concerning preoperative testicular location and 163 for preoperative testicular size. 106 of these men had levels of testosterone, inhibin B, FSH, and LH measured, while 95 of the men had semen analyses. RESULTS: Among men who had attempted paternity, there was no statistical difference in success of paternity between the previously unilateral group (89.7%) and the control group (93.7%). There was no difference in the mean time to conception (7.1 +/- 0.7 months for the unilateral group vs. 6.9 +/- 2.3 for the control group). Within the unilateral group in regard to success at paternity, no difference was found compared with the age of orchiopexy, preoperative testicular location, or preoperative testicular size. Inhibin B levels were lower among the unilateral group. FSH, LH, testosterone, sperm density, motility and morphology were not different, but considerable variation was noted within the cryptorchid group. CONCLUSIONS: In this continued evaluation of a cohort of previously cryptorchid men who had undergone unilateral orchiopexy, paternity does not appear to be significantly compromised after unilateral cryptorchidism. Unilateral cryptorchidism appears to be one of several factors contributing to infertility, similar to those found in the general population. No correlation was found between success at paternity and the age of orchiopexy, preoperative testicular size or preoperative testicular location. Inhibin B levels were lower while FSH, LH, T and sperm parameters did not differ.     

Inhibin B,follicle stimulating hormone,luteinizing hormone and testosterone during childhood and puberty in males: changes in serum concentrations in relation to age and stage of puberty

Inhibin B is a gonadal dimeric polypeptide hormone that regulates synthesis and secretion of follicle stimulating hormone (FSH) in a negative feedback loop. The aim of the present study was to determine changes in serum inhibin B, gonadotropins and testosterone concentrations during childhood and puberty in males. We studied the relationship between circulating inhibin B, gonadotropins and testosterone in serum of healthy boys during the first two years of life and then in pubertal development. Using a recently developed two-side enzyme-linked immunosorbent assay (ELISA), inhibin B levels were measured in the serum of 78 healthy boys divided into eleven age groups from birth to the end of pubertal development. In addition, serum levels of gonadotropins and testosterone were measured. Serum inhibin B, gonadotropins and testosterone increased during the first months of postnatal life. A peak in serum inhibin B and gonadotropins concentrations was observed around 3-4 months of age. There was a significant positive correlation between serum inhibin B and gonadotropins and testosterone levels during the first 2 years of life. After this early increase, serum inhibin B, gonadotropins and testosterone levels decreased significantly and remained low until puberty followed by an increase beginning with the onset of puberty. Serum levels of inhibin B reached a peak at stage G3 of puberty. Around midpuberty, inhibin B lost its positive correlation with luteinizing hormone (LH) and testosterone from early puberty, and developed a strong negative correlation with FSH, which persisted into adulthood. We conclude that inhibin B plays a key role in the regulation of the hypothalamic-pituitary-gonadal hormonal axis during male childhood and pubertal development. Inhibin B is a direct marker of the presence and function of Sertoli cells and appears to reflect testicular function in boys.     

Measurement of dimeric inhibins and effects of active immunization against inhibin alpha-subunit on plasma hormones and testis morphology in the developing cockerel

Inhibins and activins are implicated as endocrine regulators of follicle-stimulating hormone production and of testicular steroidogenesis and spermatogenesis in mammals. The potential involvement of these proteins in cockerels was investigated by measurement of circulating inhibin A, inhibin B, total inhibin alpha-subunit immunoreactivity (ir-alpha), activin A, LH, FSH, and testosterone from the juvenile state through to sexual maturity. Plasma inhibin A remained low between 6 to 12 wk of age and increased approximately threefold (P < 0.05) to a prepubertal peak between Weeks 14 to 18, followed by a gradual decline to the end of the study (Week 24). Although plasma FSH levels were not correlated to inhibin A before Week 16 (r = -0.17), they were negatively correlated from Week 18 (r = -0.49; P < 0.005). Inhibin B levels were below the assay detection limit until 16 wk of age but thereafter rose steadily in parallel with FSH (r = 0.27; P < 0.02) and testosterone (r = 0.35; P < 0.005). Thus, inhibins A and B showed divergent profiles during sexual maturation. Plasma ir-alpha levels were much higher than dimeric inhibin levels throughout, although the relative difference varied with age. Plasma activin A levels were below the assay detection at all times. Juvenile cockerels were actively immunized against a synthetic chicken inhibin alpha-subunit peptide conjugate to determine effects on plasma hormones and on testicular weight, morphology, and activin A content. Immunization generated circulating antibodies that bound (125)I-bovine 32-kDa inhibin but did not affect plasma FSH or testosterone levels at any stage of development. However, immunization reduced postpubertal plasma LH levels (P < 0.05) and promoted increased testicular weight (24%; P < 0.01) and total testicular activin A content (42%; P < 0.001) at 24 wk. Testis weight of immunized birds was positively correlated with inhibin antibody titer (r = 0.61; P < 0.05). Live weight gain was not affected by immunization. Morphometric analysis of testis sections showed that inhibin immunization had no effect on the fractional volume of the seminiferous tubule wall, seminiferous tubule lumen, or interstitial tissue area. Likewise, seminiferous tubule surface area and surface area:volume ratios were not different from controls. These findings support differential roles for inhibins A and B in regulating the pituitary-testicular axis during sexual maturation in the cockerel but highlight the need for more detailed studies to distinguish between potential endocrine and local intragonadal roles of inhibin-related peptides and to elucidate the mechanism by which immunization against inhibin alpha-subunit promotes testis enlargement without raising plasma FSH.     

Maintenance of sexual immaturity in male mice and bucks by immunization against N-terminal peptides of the follicle-stimulating hormone receptor

The follicle-stimulating hormone is one of the two pituitary hormones that control fertility in both sexes. In the male, receptors for FSH (FSHR) are only expressed on testicular Sertoli cells. FSH plays different roles during the male life; it functions as a growth factor during development and sustains spermatogenesis in adults. However, the exact role of this hormone as an initiator of male fertility is not fully understood and few data are available concerning its involvement during the peripubertal period. We recently produced filamentous phages displaying FSHR fragments overlapping residues 18-38, which, if injected in animals, induced anti-FSH receptor immunity capable of inhibiting hormone binding. We employed this strategy to transiently inhibit FSH activity in male mice and male goats of the Saanen and the Mongolian Alpas Cashmere breeds at the prepubertal stage. Anti-FSHR peptide immunization from the age of 3 wk delayed the acquisition of fecundity in male mice by up to 1 wk. Once fertile, progeny sizes produced by mating immunized males and untreated females were found to be reduced by up to 60%. In two different breeds of goats, FSHR peptide vaccines were able to maintain circulating testosterone at low prepubertal levels for several months despite no alteration in LH levels, reflecting their ability to delay the onset of puberty. These results support the conclusion that FSH may play a central role in the male at puberty through the control of testosterone production.     

Leydig cell insufficiency after testicular irradiation for acute lymphoblastic leukemia

Leydig cell function in 21 boys with acute lymphoblastic leukemia who had been treated by bilateral direct testicular irradiation (12 X 2 Gy) at 8.4 +/- 0.7 years, was evaluated 3.8 +/- 0.4 years after irradiation. At the time of irradiation all were prepubertal and at evaluation 12 were prepubertal and 9 pubertal. Leydig cell insufficiency, indicated by a low plasma testosterone response to chorionic gonadotrophin and/or an increase in basal level of plasma luteinizing hormone, was observed in 19/21 patients. The children who were the youngest at testicular irradiation were more vulnerable. Spontaneous virilization occurred in 3 of the older children and resulted from compensated Leydig cell dysfunction.     

Pubertal endocrinology of yellow baboon (Papio cynocephalus): Plasma testosterone,testis size,body weight,and crown-rump length in males

A cross-sectional study (n = 99) was made of male baboons (Papio cynocephalus) aged 3 weeks to > 10 years. Serum testosterone and testicular size were compared with body weight and crown-rump length. Pubertal onset in baboons occurs at 3–4 years of age; data were analyzed, therefore in three groups: 0–3 years; 3–4 years; and greater than 4 years. Testicular volume index increased minimally prior to 3 years of age. Between 3 and 4 years of age, there was an increase (P < .05) in testicular growth, which was followed after 4 years of age by a return to the prepubertal rate. Plasma testosterone decreased from birth to 3 years of age. Between 3 and 4 years of age, there was an increase (P < .05) in testosterone. The levels of which remained unchanged after 4 years of age. A linear increase in body weight was observed for the first 3 years which was followed by an increase (P < .05) in the rate of weight gain between 3 and 4 years of age. After 4 years of age, body weight continued to increase but at a rate less than those of the two earlier periods. A linear increase in crown-rump length was observed over the first 3 years. Between 3 and 4 years of age there was a slight increase (P > .06) in crown-rump length, which approached zero after 4 years of age. These data demonstrate many similarities between the pubertal development of male baboons and humans. Male baboons appear to be appropriate for the study of reproductive and endocrine development and the factors involved in the pubertal growth spurt of the human male.     

Testosterone reserve capacity in prepubertal and juvenile testes after sugery for undescended testis]

Tests testosterone reserve capacity of 6--15 year-old boys was estimated after operative correction of testicular maldescensus by a maximal stimulation test. Subnormal plasma testosterone levels were found in only 2 out of 14 patients with bilateral and 4 with unilateral orchidopexy. Prepubertal boys with unilateral anorchia had normal basal testosterone values and a normal testosterone rise after stimulation. In prepubertal boys with bilateral testes atrophy there was observed a diminished rise after stimulation. The basal testosterone levels were normal. The testosterone basal levels of pubertal boys with unilateral anorchia or bilateral atrophy were subnormal and the stimuation of testosterone production was reduced. The testicular volume of patients without atrophy or anorchia after orchidopexy was normal in prepuberty. During puberta a progressive relative decrease of the testicular volume was observed as compared to normal development. In conclusion, the results demonstrate that the endocrine function in most patients with unilateral or bilateral orchidopexy is in the normal range--a regular puberty can be expected.     

Macroorchidism and fragile X in mentally retarded males

Summary One hundred and seventy eight males resident in an institution for the mentally retarded were screened clinically for the presence of macroorchidism, using the standard orchidometer. In this way 52 males with a testicular volume of 25 ml and over were found. Of these, 11 had pronounced macroorchidism (above 25 ml). All 52 males were examined cytogenetically for the fragile X. Two patients with pronounced macroorchidism showed this abnormality. Although the other nine patients with pronounced macroorchidism were reexamined with FUdR-addition to blood cultures, no further cases positive for the fragile X were found. Also, the thyroid function as well as the prolactin level in serum were investigated in all 52 males. No significant abnormalities were found. The high incidence of macroorchidism in mentally retarded males is underlined; however, it is suggested that the definition of macroorchidism should take into account several parameters.     

Developmental changes in pituitary-gonadal function in free-ranging lions (Panthera leo leo) of the Serengeti Plains and Ngorongoro Crater

Pituitary-gonadal function was examined in male lions free-ranging in the Serengeti Plains or geographically isolated in the Ngorongoro Crater of Tanzania. Lions were classified by age as adult (6.1-9.8 years), young adult (3.3-4.5 years) or prepubertal (1.4-1.6 years, Serengeti Plains only). Each animal was anaesthetized and then bled at 5-min intervals for 100 min before and 140 min after i.v. administration of saline or GnRH (1 micrograms/kg body weight). Basal serum LH and FSH concentrations were similar (P greater than 0.05) among age classes and between locations. In Serengeti Plains lions, net LH peak concentrations after GnRH were approximately 35% greater (P less than 0.05) in prepubertal than in either adult or young adult animals. GnRH-stimulated LH release was similar (P greater than 0.05) between adult and young adult lions, and these responses were similar (P greater than 0.05) to those measured in Ngorongoro Crater lions. Basal and GnRH-stimulated testosterone secretion was higher (P less than 0.05) in adult than in young adult lions and lowest (P less than 0.05) in prepubertal lions. Age-class differences in testosterone production were related directly to the concentrations of LH receptors in the testis (P less than 0.05). Basal and GnRH-stimulated testosterone secretion and gonadotrophin receptor concentrations within age classes were similar (P greater than 0.05) between lions of the Serengeti Plains and Ngorongoro Crater. Lower motility and higher percentages of structurally abnormal spermatozoa were observed in electroejaculates of young adult compared to adult Serengeti Plains males (P less than 0.05) and were associated with decreased steroidogenic activity. In contrast, there were no age-related differences in ejaculate characteristics of Ngorongoro Crater lions. Seminal quality in the Crater population was poor in adult and young adult animals and was unrelated to alterations in pituitary or testicular function. In summary, only seminal quality in adult male lions was affected by location, whereas age significantly affected both basal and GnRH-stimulated testosterone secretion and seminal quality (Serengeti Plains only) in sexually mature males. The striking seminal/endocrine differences among pride (breeding) males of different ages raises questions about the impact of age on individual reproductive performance in this species.     

Effects of sport (football) on growth: auxological, anthropometric and hormonal aspects

There are very few data available on the relationship between sporting activities, endocrine levels and changes in anthropometric measurements during growth. In order to study these relationships, we have made measurements of growth, changes in physical conformation and the plasma levels of several hormones [cortisol, dehydroepiandrosterone sulphate (DHEA-S), testosterone, growth hormone, somatomedin C, insulin, glycaemia and haemoglobin A1C] in 175 boys, aged 10-16 years, who have played football at a competitive level and in 224 boys, severing as controls, who have never performed sporting activities regularly. The football players were divided into prepubertal and pubertal subjects (10-11.99 years, 12-13.99 years and 14-16 years, chronological and bone age groups). Our results showed no significant differences in the growth indices between prepubertal athletes and controls, but the plasma level of DHEA-S was significantly higher (P less than 0.05) in the athletes. Pubertal football players, however, were significantly taller than the control subjects, particularly at 14-16 years chronological age. There were no such significant differences when bone age was considered. The pubertal football players were also more advanced in all biological indices of maturity, i.e. pubic hair, testicular volume and bone age. The increase in DHEA-S in pubertal football players, already seen in prepubertals, was also combined with a significant increase in testosterone, growth hormone and cortisol levels. Thus, in football players the DHEA-S level is already higher during prepuberty. This increase thus precedes all other indices of growth and maturation associated with puberty. We hypothesize that, while not excluding the possible influence of selection, as ours is a cross-sectional study, adrenal hyperactivity may be mainly responsible for the earlier onset of pubertal growth and maturity in exercising males.     

Puberty in the male chimpanzee: time-related variations in luteinizing hormone, follicle-stimulating hormone, and testosterone

The onset of pubertal testicular growth (Po) occurred in 12 out of 20 male chimpanzees surveyed monthly for at least 3.7 yr. When animals were synchronized according to Po, the mean weight gain was found to be higher before than after Po, and testicular volume started to rise immediately after Po. The earlier significant hormonal events were a rapid rise in LH and a slight testosterone increase occurring 6 mo before Po. Thereafter, the levels of LH remained elevated while testosterone continued to rise in parallel with the testicular volume. FSH levels increased suddenly at Po, 6 mo after the LH increase. FSH remained elevated for only 9 mo, then dropped to prepubertal levels. The dissociation between onsets of pubertal increases in LH and FSH secretions suggests that the complete reawakening of the hypothalamic-pituitary unit lasts several months. The secondary drop of FSH, occurring at the time of spermarche, may be induced by factor(s) secreted by the testis.     

The role of estrogen in bone growth and maturation during childhood and adolescence

Twenty years ago it was believed that pubertal growth was stimulated by testicular androgen in boys and by adrenal androgen in girls. Estrogen, which was used to inhibit growth in excessively tall girls, was not thought to have growth-promoting effects. We hypothesized that estrogen has a biphasic effect on epiphyseal growth, with maximal stimulation at low levels. We showed that the administration of low doses of estrogen, corresponding to a serum estradiol level of about 4 pg/ml (15 pmol/l) caused more than a 60% increase over the prepubertal growth rate in both boys and girls. To test the hypothesis that estrogen is the principal mediator of the pubertal growth spurt in boys, we administered the aromatase inhibitor, testolactone, to boys with familial male-limited precocious puberty. Testolactone produced near normalization of both growth velocity and bone maturation, despite levels of serum testosterone that remained within the adult male range. The observation that low levels of estrogen stimulate growth and bone maturation suggested that estrogen might explain the more rapid epiphyseal maturation of prepubertal girls compared to boys. To determine whether prepubertal girls have higher estrogen levels than prepubertal boys, we developed an ultrasensitive recombinant cell bioassay for estrogen with a sensitivity of 0.02 pg/ml (0.07 pmol/l) estradiol equivalents. Prepubertal girls had approximately eight-fold higher levels of serum estradiol than did prepubertal boys (0.6 ± 0.6 pg/ml (SD) (2.2 ± 2.2 pmol/l) vs 0.08 ± 0.2 pg/ml (0.29 ± 0.73 pmol/l), P < 0.05). We concluded that the pubertal growth spurt of both sexes is driven primarily by estrogen, and that the more rapid epiphyseal maturation of prepubertal girls (vs boys) may be explained by their higher estradiol levels.     

Prevalence of carcinoma in situ of the testis in 207 oligozoospermic men from infertile couples: prospective study of testicular biopsies.

OBJECTIVE: To investigate the prevalence of carcinoma in situ of the testis in a group of oligozoospermic men from infertile couples. DESIGN: A consecutive group of oligozoospermic men from infertile couples were offered bilateral testicular biopsy. The observed prevalence of carcinoma in situ was compared with the expected prevalence of testicular cancer in a corresponding age matched population of Danish men, assuming all untreated cases of carcinoma in situ progress to tumour stage. This calculation was based on data from the Danish Cancer Registry. SUBJECTS: 207 men aged 18-50 years who had sperm density below 10 million/ml in two samples within the previous 2 years or sperm density below 20 million/ml in two samples within the previous 2 years and a history of cryptorchidism or one or two atrophic testicles (orchidometer volume less than 15 cm3), or both. INTERVENTIONS: Bilateral testicular biopsies. MAIN OUTCOME MEASURES: Carcinoma in situ in the biopsy specimen. RESULTS: No case of carcinoma in situ was found among the 207 men. The expected number in a normal age matched population of corresponding size was 0.8. CONCLUSIONS: There is no increase in risk of carcinoma in situ of the testis in moderately oligozoospermic men of couples referred because of infertility.     

Seasonal variation in pituitary-gonadal function in free-ranging impala (Aepyceros melampus).

Blood, testicular biopsies and electroejaculates were collected from adult male impala, free-ranging in the Kruger National Park (Republic of South Africa), during the breeding (rut; April-May) and nonbreeding (September-October) seasons. Blood samples were collected at 5-min intervals for 120 min from anaesthetized males (n = 7 impala/group) treated intravenously with saline, gonadotrophin-releasing hormone (GnRH: 1 microgram/kg body weight) or human chorionic gonadotrophin (hCG: 10 or 30 iu/kg). Semen was collected from six more animals during the breeding season and 12 animals during the nonbreeding season using a standardized electroejaculation protocol. Ejaculates obtained during the nonbreeding season were of inferior quality to those collected during the breeding season, and were characterized by lower sperm concentrations, poorer sperm motility and more morphologically abnormal sperm forms. Within season, there were no differences in testosterone secretion between the two hCG doses, and these responses were similar to those observed after GnRH, but during the rut, testosterone secretion stimulated by both GnRH and hCG was approximately nine times greater than during the nonbreeding season. This seasonal increase in testosterone production was associated with a doubling in testicular volume and concentrations of luteinizing hormone (LH) receptors. Although concentrations of testicular follicle-stimulating hormone (FSH) receptors were similar between seasons, receptor content increased during rut as a result of increased testicular volume. In contrast to testosterone secretion, basal LH and FSH secretions were unaffected by season and GnRH-induced gonadotrophin secretion was reduced during rut.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gonadotropin binding and testicular function in old rats.

Serum testosterone levels, testicular LH binding and the spermatogenic cycle were analyzed in rats 4 and 22 mo of age. With age, serum testosterone levels decreased from 3.2 to 0.63 ng/ml serum. There was no age related decline in testicular LH binding or changes in the spermatogenic cycle.     

Long-term results of long-acting luteinizing-hormone-releasing hormone agonist in central precocious puberty.

Thirty children with precocious puberty (24 girls aged 6.5 +/- 2.3 years and 6 boys aged 7 +/- 2.9 years) were treated over 5 years with Decapeptyl. In girls, the menses disappeared, breast enlargement regressed, and uterus and ovary sizes returned to prepubertal values. In boys, a significant decrease of testicular size was observed. Plasma levels of estradiol and testosterone, and basal and post-luteinizing hormone (LH)-releasing hormone (LHRH) LH and follicle-stimulating hormone (FSH) remained in the prepubertal range. Growth velocity decreased after 1 year from 9.7 +/- 3.5 to 5.5 +/- 1.3 cm/year, while the height age/bone age ratio was normalized in both sexes after 3 years. In 15 girls, Decapeptyl was interrupted after 2.3 years. During those 2.3 years, bone age increased from 11.6 +/- 0.8 to 12.5 +/- 0.7 years with a growth velocity of 5.3 +/- 1.8 cm/year. During the year following interruption, height increased from 152.2 +/- 4.9 to 157.7 +/- 4.9 cm (growth velocity 5.5 cm/year) and bone age from 12.5 +/- 0.7 to 13.5 +/- 0.6 years. One year after treatment, plasma levels of estradiol were 106.7 +/- 84.7 pg/ml, of LH, 25.5 +/- 17.6 mIU/ml, and of FSH, 10.8 +/- 5.9 mIU/ml. Menses appeared in 13 girls. Moreover, 18 months after interruption, bone age was 13.9 +/- 0.6 years and height 159.5 +/- 5.2 cm, being significantly superior to the final height of a historical control group: 151.5 +/- 4.8 cm (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Male hypothalamic hypogonadism: induction of spermatogenesis by subcutaneous pulsatile gonadotrophin-releasing hormone

Six male patients (aged 21-34 years) with isolated hypothalamic hypogonadism were given subcutaneous pulses of gonadotrophin-releasing hormone every 90 min for 14-74 weeks. The therapy produced an increase in testicular volume (4 patients) and a rise in serum luteinizing hormone, follicle-stimulating hormone, and testosterone levels in every patient. Motile sperm developed in 3 patients after a mean of 17 weeks, but were not seen in other patients who were less sexually developed after a mean of 31 weeks of therapy. Computerized tomography scans of the pituitary fossa revealed an empty sella in 4 patients and a partially empty sella in 2. Subcutaneous pulsing of gonadotrophin-releasing hormone is a simple and safe way of inducing spermatogenesis, but it is more likely to be successful in patients whose pubertal development is otherwise near completion. Previous human chorionic gonadotrophin and/or testosterone treatment does not interfere with and may benefit subsequent gonadotrophin-releasing hormone therapy.