Search

Aim To establish normal reference values for penile size in Nigerian newborn boys and to compare those values with standards from other populations. Methods A total number of 261 healthy newborn boys delivered at gestational ages of 28 weeks or more were enrolled in the study. Penile lengths and widths were measured within 72 h of birth. Results The mean (±SD) penile length in the 261 Nigerian males studied was 3.4 ± 0.48 cm, while the mean mid-shaft diameter was 1.2 ± 0.14 cm. Compared with data from other populations, Nigerian newborn boys had similar penile sizes to those reported for US Caucasian boys (mean 3.4 cm), but significantly greater penile sizes than those reported for boys from China and Hong Kong (mean 3.0 and 3.1 cm, respectively; both p < 0.001). There was a slight, but significant, difference in size between Nigerian and Malaysian boys, with Malaysian boys having greater penile sizes (mean 3.5 cm; p < 0.05). Conclusion A Nigerian newborn with a penile length of <2.39 cm can be considered to have a micropenis. [ABSTRACT FROM AUTHOR]

The importance of estrogens for the regulation of longitudinal bone growth is unequivocal. However, any local effect of estrogens in growth plate cartilage has been debated. Recently, several enzymes essential for estrogen synthesis were shown to be expressed in rat growth plate chondrocytes. Local production of 17beta-estradiol (E2) has also been demonstrated in rat costal chondrocytes. We aimed to determine the functional role of locally produced estrogen in growth plate cartilage. The human chondrocyte-like cell line HCS-2/8 was used to study estrogen effects on cell proliferation (3H-labeled thymidine uptake) and apoptosis (cell death detection ELISA kit). Chondrocyte production of E2 was measured by RIA and organ cultures of fetal rat metatarsal bones were used to study the effects of estrogen on longitudinal growth rate. We found that significant amounts of E2 were produced by HCS-2/8 chondrocytes (64.1 +/- 5.3 fmol/3 days/10(6) cells). The aromatase inhibitor letrozole (1 microM) and the pure estrogen receptor antagonist ICI 182,780 (10 microM) inhibited proliferation of HCS-2/8 chondrocytes by 20% (P < 0.01) and almost 50% (P < 0.001), respectively. Treatment with ICI 182,780 (10 microM) increased apoptosis by 228% (P < 0.05). Co-treatment with either caspase-3 or pan-caspase inhibitors completely blocked ICI 182,780-induced apoptosis (P < 0.001 vs ICI 182,780 only). Moreover, both ICI 182,780 (10 microM) and letrozole (1 microM) decreased longitudinal growth of fetal rat metatarsal bones after 7 days of culture (P < 0.01). In conclusion, our data clearly show that chondrocytes endogenously produce E2 and that locally produced estrogen stimulates chondrocyte proliferation and protects from spontaneous apoptosis. In addition, longitudinal growth is promoted by estrogens locally produced within the epiphyseal growth plate.

This report summarizes follow-up studies in 18 patients who underwent bilateral adrenalectomy for congenital adrenal hyperplasia. Three of these patients were young children with null/null mutations of CYP21, and the other 15 were adrenalectomized because of difficulties in their management on conventional therapy. The average duration of follow-up was 59 months and represents an aggregate of 90 postoperative years. The adrenals were removed laparoscopically in 13 patients and by open flank incisions in five. Adrenal crises associated with severe illnesses occurred in five patients at times when their glucocorticoid substitution was suboptimal. All were responsive to appropriate therapy. Two of these patients were young children who had hypoglycemia during gastroenteritis or febrile illness associated with poor food intake or vomiting. Significant elevations of adrenal steroid precursors, presumably from ectopic adrenal rests, were observed postoperatively in eight of the patients. Patients and parents were nearly unanimous in their enthusiasm for adrenalectomy. In most, signs of androgen excess have decreased, and obesity has become less of a problem with lowering the dose of glucocorticoid. We conclude that adrenalectomy is a safe and efficacious method of managing congenital adrenal hyperplasia in selected patients. Prophylactic adrenalectomy in young children with double null mutations remains experimental.

Apoptosis occurs in the growth plate during normal and abnormal longitudinal growth. To investigate the role of apoptosis during growth plate maturation, apoptosis and apoptosis-related proteins were studied in rat tibial growth plates at 2, 4, 8, and 11 wk of age. Apoptosis was studied by the terminal deoxynucleotidyl transferase (TdT)-mediated deoxy-UTP nick end-labeling (TUNEL) method, and immunohistochemistry was used to detect p53, caspase-3 and -6, the antiapoptotic proteins Bcl-2 and Bcl-x, and the proapoptotic proteins Bax and Bad. In all age groups studied, most apoptotic chondrocytes were terminal hypertrophic chondrocytes (THPCs) with a significant increase during development. At 2 wk, 0.108 +/- 0.026 THPCs were found to be apoptotic per millimeter of growth plate width; at 4 wk, 0.355 +/- 0.048; at 8 wk, 0.394 +/- 0.043; and at 11 wk, 1.084 +/- 0.069 (p < 0.001; 11 wk vs 2, 4, and 8 wk). THPCs were negative for p53 immunoreactivity at 2 and 4 wk, whereas some THPCs were positive at 8 and 11 wk. Caspase-3 and -6 were found in proliferative and early hypertrophic cells at 2 wk, whereas mature hypertrophic cells and THPCs were negative. At later stages of development, mature hypertrophic cells and THPCs were stained for both caspase-3 and -6. Bcl-2 and Bcl-x were present in proliferative and early hypertrophic cells at 2 wk, whereas at older ages a decrease in staining was observed. At 2 wk of age, Bax and Bad immunoreactivities were localized in proliferative and early hypertrophic cells, whereas at 8 and 11 wk many mature hypertrophic cells and THPCs were immunoreactive for Bax and Bad. Our results show that apoptosis is developmentally regulated in the rat growth plate. In older animals, with decreased growth rate and growth plate height, apoptosis is significantly increased, especially in THPCs.

Estrogens play an important role in the regulation of longitudinal bone growth in man, as demonstrated by recent descriptions of individuals with estrogen insensitivity or aromatase deficiency. Two estrogen receptors, ERalpha and ERbeta, have been cloned. The aim of the present study was to investigate the function of ERalpha in the regulation of body growth and skeletal growth. Adult female mice with inactivated ERalpha (ERalpha-/-) demonstrated an increased body weight compared with wild-type mice (114% of control). However, the length of the appendicular skeleton was decreased in adult ERalpha-/- mice (femur 93% of control). In contrast, the axial skeleton was normal (crown-rump length 98% of control). The decreased growth of the appendicular skeleton was associated with decreased serum levels of IGF-I (77% of control), indicating that the GH/IGF-I axis may be involved in the decreased longitudinal bone growth seen in female ERalpha-/- mice., (Copyright 1999 Academic Press.)

The effect of two class III antiarrhythmic drugs (Almokalant, Astra-Hässle and Dofetilide, Pfizer) on fluid secretion by rat testes has been examined. Both drugs reduced fluid secretion, whether this was measured by the amount of rete testis fluid that could be collected 22 h after unilateral efferent duct ligation, or by the difference in mass between the ligated and unligated testes, or by the difference in amount of supernatant fluid after the parenchyma of the ligated and unligated testes had been dispersed and centrifuged. The secretion of potassium, calculated from the amount of potassium in the supernatant fluids from the ligated and unligated testes was also reduced by the drugs, whereas the secretion of androgen-binding protein and inositol was unaffected. The concentration of potassium in the secreted fluid, calculated from the amount and composition of the supernatant fluids, was not affected by treatment of the rats with Almokalant, but was increased in rats treated with Dofetilide and, in these, the concentration of sodium was reduced and that of magnesium and inositol was increased and the concentration of total protein was unaffected. The concentration of androgen-binding protein in secreted fluid was increased in rats treated with Almokalant, while the concentration of testosterone was unaffected. Histological examination of testes from treated rats revealed phagocytosis of stage 19 spermatids in tubules at stages VIII-IX after 2 days, at stages IX-XI after 4 days and at stages VIII-XIV after 7 days, apparently owing to an effect on spermiation. It appears that these drugs interfere with potassium-mediated fluid secretion by the testis, leading to the other changes seen.

The secretion rate of the Sertoli-cell-specific androgen-binding protein (ABP), has been studied in isolated rate seminiferous tubules, where the stages of the spermatogenic cycle have been identified by a transillumination method. The secretion of ABP was highest in stages VII-XII, as determined by steady-state polyacrylamide-gel electrophoresis as well as by radioimmunoassay. More specifically, when the sensitive RIA technique permitted the assay of ABP secretion from a total amount of 10-30 mm of isolated tubules, it was found that maximal ABP secretion occurred at stages VIII-XI and minimal at stages IV-V. The present results show that the secretory activity of the Sertoli cells (ABP) is influenced by the type of germ cell at each cell association. It is postulated that the variation is Sertoli-cell secretory activity is of importance for the normal maintenance of spermatogenesis.

Soluble Mn2+-dependent adenylate cyclase and protein carboxyl methylase are two enzymes that are primarily localized in haploid germ cels of rat testicular tissue, and both enzymes exhibit an increase in activity in association with sexual maturation. Experimental cryptorchidism (surgery at 17 days of age) in immature rats prevented the age-dependent increase in the activity of these two testicular enzymes. After orchidopexy at 34 days of age the activities of these two enzymes increased to normal control values in association with testicular growth. These observations show that biochemical markers such as soluble Mn2+-dependent adenylate cyclase and protein carboxyl methylase can be used to follow germ cell differentiation.

When various doses of testosterone propionate (10 to 10,000 mug/day) were given to 21-day-old rats for 10 days a biphasic effect was seen both on testis weight and production of androgen-binding protein (ABP). At low doses (10 to 100 mug testosterone propionate/day) there was a reduction in testis weight as well as ABP content in the epididymis. At higher doses of testosterone propionate, there was a stimulation of both testicular weight and ABP production in spite of suppressed serum FSH and LH levels. These effects of testosterone propionate on Sertoli cell secretory function strongly suggest that the Sertoli cell is a target cell for androgen.

The cytoplasmic recptor (CR) in rat epididymal 105,000 g supernatant was separated from the androgen-binding protein (ABP) by gel electrophoresis following labeling with [1,2,6,7-3H]-testosterone in vivo. ABP disappeared from epididymal supernatants after castration of hypophysectomy, while CR remained unchanged. CR was evenly distributed between caput and cauda, while much more ABP was present in caput. Properties of CR in epididymis and prostate were similar and distinctly different from ABP. Binding to CR was destroyed by charcoal treatment (1 mg/mg protein) of supernatant for 0 degrees C for 6 h, heating at 50 degrees C for 30 min, or exposure to the sulfhydryl blocking reagent, p-chloromercuriphenylsulfonate (1mM) at 25 degrees C for 30 min, while binding to ABP was unaffected. The isoelectric pH of CR (5.8) was higher than that of ABP (4.6). Dissociation of radioactive 5alpha-dihydrotestosterone (DHT) from CR and nuclear receptors was extremely slow (half-time at 0 degrees C is greater than 2 days), while dissociation from ABP was rapid (half-time at 0 degrees C is similar to 6 min). Cyproterone acetate (250 mg/100 g body weight) inhibited binding to CR both in epididymis and ventral prostate but did not affect binding to ABP. Nuclear uptake was inhibited by cyproterone to the same extent as binding to CR, indicating that nuclear uptake and binding are dependent on CR and independent of ABP. The time-course of uptake and binding in epididymal supernatant and nuclear fractions was essentially the same 1 day after bilateral castration when both CR and ABP were present or 8 days after castration when CR alone was present. It is concluded that the cytoplasmic receptor for androgen in rat epididymis has properties very similar to the androgen receptor in ventral prostate but different from ABP.

The results of light and electron microscopic examination and of biochemical proteoglycan studies of costochondral and iliac crest biopsies from a recently diagnosed case of Dyggve-Melchior-Clausen dysplasia are reported. At light microscopy of resting cartilage large lacunae containing clusters of five or more chondrocytes were seen in some areas. In the hyaline cartilage there were scattered fibrous foci but no mineralized areas. Electron microscopy revealed chondrocytes containing widened cisternae of rough endoplasmic reticulum and vesicles coated with a smooth single-layered membrane. The content of the cisternae and of the vesicles was amorphous. Throughout the cartilage a considerable proportion of the chondrocytes displayed more or less pronounced necrobiotic changes. The biochemical analysis showed an increased amount of glucosaminoglycans in the cartilage and indicated that the ability of proteoglycan monomers to reaggregate to hyaluronic acid chains was decreased. Our findings support the suggestion that Dyggve-Melchior-Clausen dysplasia is due to a disturbance in proteoglycan metabolism.

In order to elucidate the mechanisms behind the deleterious effects on the germinal epithelium of experimental cryptorchidism the hypothesis that a leaking blood-testis barrier is the cause of the damage was tested. The permeability of the specialized inter-Sertoli cell junctions to lanthanum after experimental cryptorchidism for 0.5 to 12 days was studied in the rat. In none of the time periods studied lanthanum had penetrated beyond the inter-Sertoli cell junctions. A simple lanthanum immersion technique was used. Testes of 15-days old rats (before the development of the barrier) were used as a positive control of the method, and in these testes lanthanum had penetrated up to the future lumen.

The production of testicular androgen-binding protein (ABP), as a measure of Sertoli cell function, was studied after unilateral or bilateral experimental cryptorchidism in adult rats. Two or 4 weeks after the testis had been translocated to the abdomen, no major changes were found in the concentration of ABP per mg protein, although there was a marked and progressive decrease in ABP content per testis. However, the rate of ABP production was greatly decreased, as measured by the accumulation of ABP during 16-h ligation of the efferent ducts or by the production of ABP by testis mince in an in vitro system. This indicates that the Sertoli cell function is severly impaired by the intra-abdominal position.

The stage-specific influence of the secretions from rat seminiferous tubules on the LH-stimulated testosterone production by rat Leydig cells in vitro was studied. The spent media from incubated seminiferous tubules (SMST) from stages VII-VIII of the seminiferous epithelial cycle caused about 50% inhibition of the LH-dependent testosterone production by a crude preparation of rat interstitial cells. The SMST from other stages had no effect on testosterone production. Mixed tubules of unidentified stages gave an intermediate response. When SMST from ten different stages of the seminiferous wave were compared, the most pronounced inhibitory activity was found in stages VI and VIII-XI, while SMST from stages I, VII and XIII-XIV had no inhibitory effects on interstitial cell testosterone production. No stimulation was found in this system. Prolonged incubation of the interstitial cells with SMST from stages VIII-XI resulted in loss of inhibitory activity after 12 h of incubation. Maximum inhibitory activity was noted after 3 h of incubation. The inhibitory activity of the SMST from stages VIII-XI was retained after prolonged dialysis, and was unchanged after heating the medium at 60 degrees C for 1 h. The activity did not seem to be due to the presence of proteolytic enzymes, since it was not influenced by addition of protease inhibitors. SMST from stages VIII-XI had no effect on the metabolism of [3H]testosterone added to the interstitial cell preparations. No inhibitory effect was observed when Leydig cells were incubated with dibutyryl cAMP instead of LH, suggesting an early influence on the LH-receptor-adenylate cyclase chain of events.(ABSTRACT TRUNCATED AT 250 WORDS)

Production of testicular androgen binding protein (ABP), ceases following hypophysectomy and can be stimulated by FSH. Within 24 h after the administration of FSH, ABP can be measured in caput epididymis supernatant and by 4 days after FSH treatment, the concentration of ABP reaches a plateau. In a 3-day assay, ABP production in immature hypophysectomized rats was stimulated by 31 mug NIH-FSH-P1 per day (0.08 U NIH-FSH-P1 per 3 days) which is comparable to the sensitivity of the ovarian weight augmentation test in hypophysectomized rats. The relative ovarian weight augmenting and ABP stimulating activities of various FSH preparations were in agreement, suggesting that the biological stimulus of the ABP response is, in fact, FSH. The ABP response to FSH could become a useful testicular bioassay for FSH. Such an assay would be more practicle if ABP could be measured by a radioimmunoassay.