Normal Age Of Puberty Research Articles

Clinical Characteristics and Growth Hormone Treatment in Patients with Prader-Willi Syndrome

Objective:To investigate clinical characteristics and response to growth hormone (GH) treatment in patients with Prader-Willi syndrome (PWS) in Turkey.Methods:The data of 52 PWS patients from ten centers was retrospectively analyzed. A nation-wide, web-based data system was used for data collection. Demographic, clinical, genetic, and laboratory data and follow-up information of the patients were evaluated.Results:The median age of patients at presentation was 1.5 years, and 50% were females. Genetic analysis showed microdeletion in 69.2%, uniparental disomy in 11.5%, imprinting defect in 1.9% and methylation abnormality in 17.3%. Hypotonia (55.7%), feeding difficulties (36.5%) and obesity (30.7%) were the most common complaints. Cryptorchidism and micropenis were present in 69.2% and 15.3% of males, respectively. At presentation, 25% had short stature, 44.2% were obese, 9.6% were overweight and 17.3% were underweight. Median age of obese patients was significantly higher than underweight patients. Central hypothyroidism and adrenal insufficiency were present in 30.7% and 4.7%, respectively. Hypogonadism was present in 75% at normal age of puberty. GH treatment was started in 40% at a mean age of 4.7±2.7 years. After two years of GH treatment, a significant increase in height SDS was observed. However, body mass index (BMI) standard deviation (SDS) remained unchanged.Conclusion:The most frequent complaints were hypotonia and feeding difficulty at first presentation. Obesity was the initial finding in 44.2%. GH treatment was started in less than half of the patients. While GH treatment significantly increased height SDS, BMI SDS remained unchanged, possibly due to the relatively older age at GH start.

Endocrinopathies in adolescents with thalassaemia major receiving oral iron chelation therapy

Background: Endocrinopathies are common in patients with thalassaemia major (TM) despite parenteral iron chelation therapy with deferoxamine. There are only a few studies on the efficacy of oral deferiprone in preventing endocrine dysfunction.Aim: To determine the growth and endocrine complications in children with TM receiving oral iron chelation with deferiprone.Methods: All adolescents with TM receiving regular blood transfusion and deferiprone were evaluated prospectively for growth and pubertal status over a 1-year period. Tests for endocrine function included oral glucose tolerance test, calcium, phosphate, alkaline phosphatase, parathyroid hormone and thyroid profile and, in those with delayed/arrested puberty, sex steroids and gonadotropins. Clonidine-stimulated growth hormone (GH) was measured in patients with height ≤−3 SD.Results: 89 patients [51 males, 38 females, mean (SD) age 13·6 (2·5) years] were evaluated. Mean (SD) pre-transfusion haemoglobin was 9·2 (1·1) g/dl and the mean (SD) age of starting deferiprone was 5·1 (2·4) years. Mean (SD) ferritin was 9159 (3312) pmol/L (normal <2247). 49 (55%) subjects were of short stature and 25 (27%) had a height Z-score ≤ −3. GH testing was performed in 19 patients, of whom 17 had peak GH values <10 μg/L. Delayed puberty and/or hypogonadism was present in 54·1% patients at or beyond the age of normal puberty. Impaired glucose tolerance/diabetes mellitus, hypoparathyroidism and primary hypothyroidism (subclinical) were present in 13·0%, 10·1% and 8·9%, respectively. Overall, 44 (49·4%) adolescents had at least one endocrinopathy.Conclusion: Adolescents with TM on oral iron chelation therapy with deferiprone experienced a high prevalence of growth faltering and endocrinopathies which was comparable to that previously reported with deferoxamine. A combination of deferoxamine and deferiprone may be necessary to prevent growth and endocrine problems.

Turner Syndrome: Updating the Paradigm of Clinical Care

Turner syndrome (TS), in which there is loss of all or part of one sex chromosome, occurs in one in 2500 live-born females and is associated with characteristic findings. Detailed healthcare checklists and screening guidelines are commonly used to detect known complications affecting individuals with TS. Even with the use of these guidelines, there remains an increased morbidity and mortality seen in TS as compared to the general population, leading to significant controversy on optimal management of several aspects of TS. A PubMed search of articles from the past 15 yr identified available studies related to the diagnosis and management of common issues related to TS as well as important historical articles. This review summarizes studies through January 2012 and highlights recent developments. There remain many areas of uncertainty in the diagnosis and management of TS. Generalizations from experience in the care of other conditions in isolation (such as poor growth, follow-up of cardiac disease, or the treatment of ovarian failure) cannot be broadly applied when caring for individuals with TS. Specific differences include treatment of growth failure as early as possible; acquisition of adequate baseline cardiac studies, followed by serial magnetic resonance imaging, targeted to identify findings unique to TS that address the increased risk of aortic dissection; initiation of hormone replacement at the normal age of puberty, preferentially with transdermal estradiol; and detailed patient counseling to explain the long-term health risks commonly associated with this disorder. A revised paradigm of care using a standardized multidisciplinary evaluation, supplementing screening tests as advocated by expert opinion guidelines, can aid clinicians in interpreting the results of diagnostic testing in the context of TS. This approach optimizes medical care for women with TS and may reduce the increased morbidity and mortality currently seen in this population.

Male acquired hypogonadotropic hypogonadism: Diagnosis and treatment

Acquired hypogonadotropic hypogonadism (AHH), contrary to congenital hypogonadotropic hypogonadism (CHH) is characterized by postnatal onset of disorders that damage or alter the function of gonadotropin-releasing hormone (GnRH) neurons and/or pituitary gonadotroph cells. AHH thus prevents the establishment of gonadotropin secretion at puberty, or its post-pubertal maintenance. Thus, postnatal AHH may prevent the onset of puberty or appear during pubertal development, but it usually emerges after the normal age of puberty. Although pituitary tumors, particularly prolactinoma, are the most common cause, sellar tumors or cyst of the hypothalamus or infundibulum, infiltrative, vascular, iron overload and other disorders may also cause AHH. Pituitary surgery and head trauma or cranial/pituitary radiation therapy are also usual causes of AHH. The clinical manifestations of AHH depend on age of onset, the degree of gonadotropin deficiency, the rapidity of its onset and the association to other pituitary function deficiencies or excess. Men with AHH have less stamina, decreased libido, erectile dysfunction and strength, and a worsened sense of well being leading to degraded quality of life. The physical examination is usually normal if hypogonadism is of recent onset. Diminished facial, body hair and muscle mass, fine facial wrinkles, gynecomastia, and hypotrophic testes are observed in long-standing and complete AHH. Spermatogenesis is impaired and the volume of ejaculate is decreased only when gonadotropins and testosterone levels are very low. Men with AHH may have normal or low serum LH and FSH concentrations, but normal gonadotropin values are inappropriate when associated with low serum testosterone. In the majority of AHH patients, serum inhibin B is “normal”. The decrease of this sertolian hormone indicates a long-standing and severe gonadotropin deficiency. Symptoms, usually associated with significant testosterone deficiency in men with AHH, improve with testosterone replacement therapy. Replacement therapy is often simple, using an injectable testosterone ester as first line treatment. Fertility can be restored rather quickly, provided there is no independent primary testicular damage and the partner is fertile.

Recombinant human growth hormone in the treatment of Turner syndrome

Turner syndrome (TS) is a common chromosomal disorder in women that is associated with the absence of one of the X chromosomes. Severe short stature and a lack of pubertal development characterize TS girls, causing psychosocial problems and reduced bone mass. The growth impairment in TS seems to be due to multiple factors including an abnormal growth hormone (GH) - insulin-like growth factor (IGF) - IGF binding protein axis and haploinsufficiency of the short stature homeobox-containing gene. Growth hormone and sex steroid replacement therapy has enhanced growth, pubertal development, bone mass, and the quality of life of TS girls. Recombinant human GH (hGH) has improved the height potential of TS girls with varied results though, depending upon the dose of hGH and the age of induction of puberty. The best final adult height and peak bone mass achievement results seem to be achieved when hGH therapy is started early and puberty is induced at the normal age of puberty in a regimen mimicking physiologic puberty. The initiation of estradiol therapy at an age-appropriate time may also help the TS patients avoid osteoporosis during adulthood. Recombinant hGH therapy in TS seems to be safe. Studies so far show no adverse effects on cardiac function, glucose metabolism or any association with neoplasms but research is still in progress to provide conclusive data on long-term safety.

Syndrome d'interruption de la tige pituitaire

Pituitary stalk transection is a non-negligible cause of growth hormone (GH) deficiency. We studied 22 children (13 boys, nine girls) aged at the first clinical manifestations from 2 days to 10 years (average = 5.33 +/- 2 years). Pituitary stalk transection was assessed by the means of magnetic resonance imaging (MRI). The children's past history showed fetal distress in 12 cases (54.5%), cranial trauma in three (13%) and a midline anomaly in three (13%). The first clinical manifestations were neonatal hypoglycemia (two cases), decreased growth velocity (18 cases) and diabetes insipidus (two cases). GH deficiency was complete, present from the onset in 19 of 22 cases and isolated in four. Fifteen of 22 cases had adreno-corticotrophic hormone (ACTH) and thyroid stimulating hormone (TSH) deficiency. Diabetes insipidus was present in six cases and revealed the syndrome in two. All children older than normal age of puberty (n = 10) had gonadotropin deficiency. In our study, these hormonal anomalies progressed from isolated GH deficiency to multiple hormonal deficiencies. The recently described stalk transection syndrome is relatively frequent and should be suspected after cranial trauma or fetal distress syndrome. The outcome is progressive evolution towards panhypopituitarism and these patients require regular clinical survey and hormonal controls.

Regional differences in the distribution of gonadotropin-releasing hormone cells between rapidly growing and growth-restricted prepubertal female sheep.

Growth retardation induced by dietary restriction in the lamb results in a low GnRH pulse frequency, and thus, puberty is delayed. In our experimental model, in which ovariectomized lambs are maintained at weaning weight (approximately 20 kg BW), hypothalamic GnRH is present and releasable, suggesting that central mechanisms limit the release of GnRH during chronic growth restriction. Our study compared the number and distribution of GnRH-containing neurons in growth-restricted (n = 5) and rapidly growing (n = 5) ovariectomized prepubertal female lambs at 24 weeks of age (normal age of puberty is about 30 weeks). Immunoreactive cells were labeled using LR-1 antiserum (R. Benoit) and an avidin-biotin-immunoperoxidase procedure. GnRH neurons were localized in 60-micron coronal sections from the level of the diagonal band of Broca to the mammillary bodies. The estimated total number of GnRH neurons in the growth-restricted and rapidly growing lambs was similar (3364.8 +/- 513.8 vs. 3151.2 +/- 279.8, respectively). In addition, the percent distributions of GnRH neurons in the diagonal band of Broca, the anterior hypothalamus, the lateral hypothalamus, and the posterior hypothalamus were not different. A trend (P = 0.07) toward a smaller percent distribution in the preoptic area was noted in growth-restricted lambs (30.6 +/- 3.6) compared to rapidly growing lambs (44.0 +/- 5.2). By contrast, the percent distribution of GnRH neurons in the medial basal hypothalamus was significantly greater in the growth-restricted lambs compared with the rapidly growing lambs (17.7 +/- 2.2 vs. 6.7 +/- 1.4, respectively; P < 0.005). It is of interest that the percent distribution of GnRH-containing neurons in the medial basal hypothalamus of the hypogonadotropic growth-restricted lamb is similar to that observed in the fetal lamb, whereas the eugonadotropic rapidly growing lamb is more similar to the adult female. In this context, decreased GnRH secretion and delayed puberty during diet-induced growth restriction may arise from alterations in the GnRH neurosecretory system.

Age as a determinant of the impact of growth hormone therapy on predicted adult height

Final adult height is determined by both childhood and pubertal growth. The later is a function of growth velocity and bone maturation, and both are regulated by growth hormone. In a study of the safety and efficacy of GH therapy, we analysed the impact of age on bone maturation and predicted adult height. The subjects were 65 male patients with GH deficiency, as diagnosed by pharmacological or physiological tests, who participated in a multicentre trial and completed 3 years of hGH therapy. The age range at initiation of therapy was 3.1-15.7 years. Subcutaneous injections of hGH were given in a dose of 0.3 mg/kg/week, in thrice-weekly doses. Calculation of the adult height prediction was performed on annual growth parameters using the Bailey-Pinneau, TW-II and Roche methods. The rate of pubertal advancement correlated positively with the child's age at initiation of therapy. The bone age advanced in positive correlation with chronological age, and by the end of 3 years of hGH therapy the delta-bone age/delta-chronological age ratio increased to 1.5 for children with an age at start of therapy of 10.7 years. During the adolescent years, the predicted gained height over 3 years of therapy declined, in correlation with age, and became negative at a therapy-initiation age of 12.9 years. In a retrospective analysis of a group of children with heterogeneous GH secretory ability, GH induced acceleration of growth, around the age of normal puberty, advanced the age of pubertal onset and accelerated pubertal progression which, in turn, expedited bone maturation and thereby restricted predicted adult height gain from hGH therapy.

Hypoxanthine phosphoribosyl transferase deficiency, haematopoiesis and fertility in the mouse

We have looked for effects of deficiency in hypoxanthine phosphoribosyl transferase (HPRT) in the mouse comparable to non-behavioural consequences of HPRT-deficiency in humans. HPRT-deficient humans show abnormalities in haematopoiesis and, in heterozygotes, there is strong selection in haematopoietic tissues against HPRT-deficient cells arising as a result of X-chromosome inactivation. We have examined two situations in mice in which HPRT- and HPRT+ cells occur in the same individual. First, in chimaeras resulting from the injection of HPRT- embryonal stem cells into HPRT+ blastocysts the fate of HPRT- and HPRT+ cell populations was monitored by their expression of different isozymes of glucose phosphate isomerase and also, in those chimaeras that resulted from injecting the male ES cells into female blastocysts, by in situ hybridisation using a Y-chromosome-specific repetitive DNA probe. There was a small statistically significant selection against the HPRT- population in haematopoietic tissues in both XX in equilibrium with XY and XY in equilibrium with XY chimaeras. Second, in female mice doubly heterozygous for HPRT-deficiency and for an electrophoretic variant of the X-linked enzyme phosphoglycerate kinase, there was a similar small statistically significant selection against the HPRT- population in haematopoietic tissues. While further work is required to establish whether this selection is a consequence of the HPRT mutation, it is clear that any selection against cells in the haematopoietic system as a consequence of HPRT-deficiency is at most small compared with the effect seen in humans. In HPRT-deficient human males surviving beyond the normal age of puberty, there is testicular atrophy. However, we find no effect of HPRT-deficiency on the fertility of either male or female mice. Thus, as with effects on behaviour, the consequences of HPRT-deficiency for haematopoiesis and testis development in the mouse are at most small compared with those in the human. We conclude that the reason for the difference in effects between the two species lies in a difference in purine-related intermediary metabolism per se, rather than in its interaction with brain amine biochemistry.

Postpubertal Maturation of Endogenous Opioid Regulation of Luteinizing Hormone Secretion in the Female Sheep1

This study investigated whether the role of endogenous opioid peptides in the suppression of LH secretion during seasonal anestrus in the sheep changes with age. The experimental approach was to determine the effect of blockade of opioid receptors with naloxone on LH secretion at different times of year within the anestrous season, and to compare responses between seasonally anestrous sheep of different ages. Sheep, all past the normal age of puberty, were ovariectomized before the study and treated s.c. with estradiol implants to provide a fixed estradiol feedback signal. One-year-old females responded to naloxone with a rapid increase in LH pulse frequency in the early (April) and late (August) phases of their first anestrous season. This response was similar to that previously found in prepubertal female sheep. Only 5 of the 8 females responded to the same naloxone challenge in mid anestrus (June), suggesting that the contribution of opioid pathways to the inhibition of LH secretion at this time of year is not necessarily the same as that in early and late anestrus. None of the older anestrous sheep (greater than or equal to 2 yr) responded to naloxone in June, indicating age-related changes in the role of endogenous opioid mechanisms in the inhibition of LH secretion. Ovary-intact mature sheep did not respond to naloxone, in contrast to our previous observations in intact prepubertal females. We infer that the neural mechanisms underlying the superficially similar hypogonadotropic states that occur during the prepubertal period, first anestrous season, and later anestrous seasons are not identical.(ABSTRACT TRUNCATED AT 250 WORDS)

CLINICAL REVIEW 14 Pathophysiology and Treatment of Sexual Precocity

The complex maturational changes in both organization and activation of the hypothalamic GnRH-pituitary gonadotropin-gonadal system can be viewed as a continuum extending from its ontogeny in the fetus, through puberty, to the attainment of full sexual maturation and fertility. Restraint of the onset of puberty resides in the central nervous system (1, 2). All of the other components which include the hypothalamic GnRH pulse generator, pituitary gland, gonads, and sex steroid target organs can be activated by the appropriate stimulus at any stage between infancy and the normal age of puberty. Reactivation of the GnRH pulse generator induces increased GnRH secretion, stimulation of the pituitary gonadotropes, and subsequently increased secretion of gonadal steroids. Increased nighttime pulsatile release of LH both in frequency and amplitude and increased LH response to administration of GnRH occur with the onset of puberty. An independent process regulated by a different mechanism results in the increase i...

DEVELOPMENTAL PATTERN OF PLASMA SEX STEROID BINDING PROTEIN (SBP) IN THE ANDROGEN INSENSITIVITY SYNDROME (AIS): PUBERTAL CHANGES INDEPENDENT OF SEX STEROIDS ?

SBP was measured by a solid phase method in 80 plasma samples from 24 AIS subjects 1 mo-17 yr old. Results (μg/l) were compared to those found in 375 normal males matched for age. Weight was normal for height in all. In AIS infants, SBP was in the normal range. In AIS children, mean (±SD) SBP levels were 18.7±3.5 at 1-9 yr, and 14.4±5.3 at 11-13 yr, similar to that in normals (19.8±7.5 and 15.7±8.1). Values at 15-17 yr (13.1±5.6) were significantly (p<0.02) lower than at 1-9 yr, but higher than in normals matched for age (9.2±4.2) or testosterone (T) levels. A significant (p=0.03) correlation between SBP and age was found at 8-17 yr, but not before. These results are in general accordance with that of Cunningham et al. (JCEM, 1984, 58, 915) who reported at 38-46% fall in SBP in 2 AIS patients 8-16 yr old. The mean % fall is less in our larger series. In addition, we observed large indidual variations, both in absolute values and in the degree of changes. This was even more evident in the longitudinal study made in 6 AIS patients: a significant correlation with age was found in only 3. In conclusion: 1) In AIS infants and children SBP is in the normal range. 2) After puberty, SBP is significantly higher in AIS than in normals. 3) At the normal age of puberty, mean SBP plasma levels fall of 30% in AIS patients versus 55% in controls; this difference may account for the influence of T in normal subjects. Assuming that in AIS, T is inactive on hepatic cell as in other target cells, then about half of the pubertal fall in SBP in not T-mediated.

Evidence for Activation of the Central Nervous System-Pituitary Mechanism for Gonadotropin Secretion at the Time of Puberty in the Male Rat*

During sexual development in the male rat, serum testosterone (T) levels increase markedly at 45-60 days of age. At the time of the pubertal rise in T levels, activation of the hypothalamic-pituitary axis is difficult to demonstrate, since there is little change in serum LH levels and a decrease in serum FSH levels. We determined whether experimental maintenance of stable pubertal T levels in these animals as they passed through the normal age of puberty would allow demonstration of a major increase in serum gonadotropin levels. At 14-15 days of age, male rats were castrated and outfitted with either T-containing or empty Silastic capsules. Another group of rats was left intact and outfitted with empty capsules. At various times between 29 and 58 days of age, blood was drawn for measurement of serum LH, FSH, and T levels. In the T-implanted castrated rats, serum T levels were comparable to those in midpubertal intact rats, without significant differences among age groups. In this setting of stable T levels, serum LH and FSH were suppressed to levels at or below those in pubertal intact rats until 51 days of age, when they increased significantly into the untreated castrate range. In contrast, untreated castrate animals demonstrated markedly reduced serum T and elevated LH and FSH levels that did not change significantly throughout the entire study. In intact rats, serum T levels were stable until 58 days of age, when they increased over 2-fold; serum LH levels did not change significantly with age, and serum FSH levels decreased significantly by 54 days of age. A separate group of rats was castrated and outfitted with T-containing Silastic capsules at 21 days of age. In these animals, there were significant increases in hypothalamic LHRH, norepinephrine (NE), and dopamine levels and NE turnover rate at 56 compared to 36 days of age. We conclude that stable pubertal levels of T are able to suppress gonadotropin levels in castrated rats until the normal age of puberty, at which time LH and FSH levels increase markedly. This decrease in sensitivity of the hypothalamic-pituitary axis to T negative feedback at puberty is accompanied by increases in hypothalamic LHRH, NE, and dopamine levels and NE turnover rate. These results provide direct evidence for activation of the central nervous system-pituitary mechanism regulating gonadotropin secretion at puberty in the male rat.(ABSTRACT TRUNCATED AT 400 WORDS)

The testicular feminization syndrome

The testicular feminization syndrome is one of abnormal sex differentiation or ‘intersex’ in 46 XY males who possess testes and develop a feminine phenotype. The syndrome has a familial predisposition without a clear pattern of inheritance and affects 46 XY conceptuses without a known counterpart affecting a female 46 XX conceptus. The Y chromosomal influence on the primitive gonadal tissue is shown by testes formation, Mullerian duct inhibition hence the absent uterus and tubes, but the formed testes remain foetal in structure and poorly functional. Consequent to inadequate testosterone production, the urogenital sinus fails to differentiate into scrota1 sacs and a penis and instead forms into flat labia and a blind, shallow vagina. There is no clear reason for the testes to remain foetal and poorly functional and neither is there an obvious explanation for the absence of axillary and pubic hair although genetic deficiencies have been mentioned. The assigned sex and sex of rearing is female. They should be encouraged to lead normal lives although they remain barren. Surgical excision of the testes is recommended for fear of malignancy, preferably performed after the age of normal puberty and oestrogens substituted as a cosmetic measure.

Role of the ovaries in maturation of the estradiol-luteinizing hormone negative feedback system of the pubertal rat.

ABSTRACT. The question of whether ovaries are essential for maturation of the estradiol-LH feedback system was examined. Plasma LH concentrations of rats ovariectomized (ovx) prior to puberty and infused with estradiol (E2) before puberty were compared to those of rats ovx either before or after puberty and infused after the normal age of puberty (31–38 days of age). The rats were fitted with indwelling venous catheters so that plasma LH levels could be measured by radioimmunoassay longitudinally in individual animals and E2 could be administered as a virtually continuous infusion for 1–2 weeks. The prepubertal rats were ovx at 8 or 19 days of age and infused before puberty at 25–30 days of age. Rats infused after the normal age of puberty were ovx either before puberty at 19 days of age and infused postpubertally at 41–43 or 51–58 days of age, or ovx after puberty at 60–75 days of age and then infused one week later, at 67–82 days of age. Blood samples were obtained daily between 0930–1130 h and from som...

Hormonal modification of sexually dimorphic behavior

1. Female animals exposed to stimulation by testosterone in utero or very soon after birth may exhibit changes in adult mating behavior which are indicative of two independent types of modification. One is defeminization, and another quite different one is masculinization. The behavioral modifications are believed to represent changes in separate neural mechanisms, either of which can be altered without changing the other. The implication is, of course, that the CNS is originally bisexual with respect to its behavioral potential. 2. Independent changes which can be produced in males by eliminating the effects of endogenous testosterone during early development are demasculinization and/or defeminization. Here again, separate neural mechanisms are postulated. 3. In rodents and carnivores there are at least two types of behavior which are normally dimorphic in adulthood and are subject to modification by manipulation of androgenic stimulation during very early development. One type, represented by mating behavior, depends heavily upon concurrent hormonal stimulation in adulthood during the time it is being manifested. The other, represented by urination behavior in female dogs, is hormonally modifiable in utero but independent of gonadal hormones in adulthood. Female dogs genitally masculinized by testosterone pre- and neonatally exhibit male mounting responses as adults but only if they are injected with testosterone propionate before and during the time of testing. The same females display the male urination pattern as adults, but this behavior occurs without any concurrent androgenic stimulation and is in fact unaffected by testosterone injections. It would appear that certain sex differences in behavior which normally appear at the time of puberty are dependent upon both prenatal and pubertal hormonal action, whereas other differences may depend only upon hormonal action during development and emerge at the normal age of puberty without any additional endocrine facilitation.

Serum gonadotropin in concentrations in agonadal children and adults.

ABSTRACT Serum FSH concentrations were elevated above the age-specific normal range in all of 51 agonadal subjects ranging in age from 2 months to 22 yr. Serum LH levels were also elevated in most of these subjects. Although serum gonadotropin concentrations were above normal in the 18 infants and children, levels were significantly higher in subjects who were above the normal age of puberty. No significant differences in serum testosterone and estradiol concentration could be demonstrated between castrate and normal children. The data provide further evidence for a dynamic hypothalamic-pituitary-gonadal feedback relationship during childhood. The identity of the gonadal product responsible for the feedback inhibition is not clear. The further increment in serum gonadotropin concentrations after the normal age of puberty in agonadal subjects suggests that the changes in the hypothalamic “gonadostat” during normal puberty may occur in the absence of a functional gonad.

The effect on subsequent fertility of temporary cryptorchidization in Swiss white mice.

A series of fertile male mice were rendered temporarily cryptorchid by abdominal fixation of the testes. At intervals the testes were released in pairs of mice and the time noted when subsequent fertility returned. This was found to be about 2 months in most cases but mice with abdominal testes for more than 5 months did not always resume fertility.Similarly neonatal mice had their testes secured in the abdomen and released at intervals. Fertility returned in about 2 months if the testes were released before 2 months after the normal age of puberty. Litters which were produced in both groups were normal.The histological appearance of the testes was similar to that described in the literature.It was concluded that mice previously fertile can resume normal fertility after temporary cryptorchidization for up to 5 months. But mice cryptorchidized from birth only become fertile if the testes are placed in the scrotum before or shortly after puberty.