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PubMed1984

Human chorionic gonadotropin testing. Changing testicular response in infants with microphallus and gonadotropin deficiency.

The evaluation of microphallus often includes human chorionic gonadotropin (HCG) stimulation to evaluate testicular androgen production. The response in testosterone secretion after five days of stimulation with chorionic gonadotropin is abnormal in patients with either primary testicular defects or gonadotropin deficiency. The testes of gonadotropin-deficient children do respond if the chorionic gonadotropin therapy is continued for six weeks. The current study reports a normal response to the short course (five days) of chorionic gonadotropin therapy in two 2-month-old patients with XY chromosomes with microphallus whose clinical course and repeated testing at age 3 or 4 years indicated gonadotropin deficiency. The normal response in the neonatal period is probably the result of maternal chorionic gonadotropin priming of the fetal testes in utero. These results indicate that HCG testing is an unreliable method for identifying gonadotropin deficiency in the neonatal period.

Abnormalities, Multiple↗
PubMed1985

Effects of photoperiod, pinealectomy and castration on body weight and daily torpor in Djungarian hamsters (Phodopus sungorus).

During the autumn and winter Djungarian hamsters (Phodopus sungorus) exhibit regression of the gonads, development of a white winter pelage, loss of body weight and daily torpor. These seasonal events are largely regulated by changes in photoperiod. The present experiments were designed to examine the role of the testes and the pineal gland in photoperiodically induced daily torpor and body weight loss. Hamsters displayed a loss of body weight and daily torpor when exposed to a short-day photoperiod in a cold environment, but these phenomena did not occur in hamsters exposed to long days and cold. Testicular regression is probably a precondition for the display of torpor, since daily torpor was almost totally inhibited in hamsters which were exposed to short days and in which testosterone was administered from subcutaneous silicone elastomer implants. Nevertheless, decreased testosterone secretion alone is not a sufficient condition for induction of daily torpor, since torpor was rarely observed in hamsters exposed to long days, even after castration. In addition to decreased testicular activity, the pineal gland is also involved in establishing conditions for torpor. Thus, pinealectomy prevented the display of torpor by castrated hamsters exposed to short days. Body weight changes were also found to be influenced by both testicular hormone and pineal activity. These observations indicate that the pineal gland is involved, as a part of the photoperiodic mechanism, in regulating a variety of physiological events and that some of these actions of the pineal are independent of its extensively described actions on the reproductive axis.

Adaptation, Physiological↗
PubMed1997

A study of the relative roles of follicle-stimulating hormone and luteinizing hormone in the regulation of testicular inhibin secretion in the rhesus monkey (Macaca mulatta).

The purpose of this study was to examine the relative roles of FSH and LH in stimulating testicular inhibin secretion in the male rhesus monkey. Recombinant human (rh) FSH and rhCG were used as the gonadotropic stimuli, and juvenile rhesus monkeys, in which the endocrine activity of the pituitary-testicular axis was being driven in an adult manner with an intermittent i.v. GnRH infusion, were studied. Immunoactive inhibin levels were measured by the Monash RIA. Initiation of an intermittent i.v. infusion of rhFSH (10 IU every 3 h) resulted, after a delay of 5-6 h, in a progressive increase in the concentrations of immunoactive inhibin, which achieved, after 48 h of stimulation, a value twice that observed during vehicle treatment. Gel filtration chromatography revealed that the FSH-induced elevation in immunoactive inhibin was the result of an increase in three distinct mol wt fractions: peak I (100 kDa), peak II (50-60 kDa), and peak III (31 kDa). Although peak III accounted for most of the inhibin immunoactivity in vehicle-treated animals, peaks I and II were most responsive to FSH stimulation. Application of recently developed enzyme-linked immunosorbent assays for inhibin B and pro-alpha-C-related peptides provided additional insights into the nature of the FSH-sensitive forms of circulating immunoactive inhibin. Most notably, the 31-kDa fraction (peak III) was comprised of inhibin B and pro-alpha-C. In contrast to FSH stimulation, an intermittent infusion of rhCG (40 IU every 3 h), which markedly elevated testicular testosterone secretion, failed to increase immunoactive inhibin concentrations. These findings indicate that various forms of immunoactive inhibin are present in the circulation of the rhesus monkey, and that in this species, FSH is the principal stimulus of the secretion of testicular inhibins, including inhibin B. Additionally, they further underline the importance of the FSH-inhibin feedback loop in governing testicular function in primates.

Animals↗
PubMed1992

New hormone-related markers of high risk to breast cancer.

New markers of increased risk to breast cancer are examined and related to established risk markers. The following new evidence is highlighted: (1) Increased testosterone secretion by the ovaries is currently the only major steroid abnormality shown to be associated with increased risk of both premenopausal and postmenopausal breast cancer. (2) Upper body-type obesity is a marker for both hyperandrogenaemia and hyperinsulinaemia and is associated with an increased risk of breast cancer. Upper body type obesity may already be recognised in early puberty in caucasian girls and is associated with a characteristic androgen/oestrogen profile. (3) Relative tallness in women is associated with an increased risk of breast cancer. A hypothesis is offered on the significance of these markers in the aetiology of mammary cancer in women, and also a means of testing the hypothesis. The hormonal promotion of mammary carcinogenesis is likely to be greatest between puberty and the first full term pregnancy. The presence of hyperinsulinaemia can increase the ovarian production of androgen, and the abnormal hormonal profile may stimulate proliferative activity in mammary epithelium. This may increase the risk of epithelial atypia and carcinogenesis.

Age Factors↗
PubMed1998

Tumor necrosis factor-alpha inhibits leydig cell steroidogenesis through a decrease in steroidogenic acute regulatory protein expression.

The aim of the present study was to identify the sites of the inhibitory action of TNFalpha (tumor necrosis factor alpha) on LH/hCG-stimulated testosterone formation. By using cultured porcine Leydig cells as a model, TNFalpha was shown to inhibit testosterone secretion when testicular cells were stimulated with hCG but not when incubated with 22R-hydroxycholesterol (a cholesterol substrate derivative that readily passes through cell and mitochondrial membranes). Such an observation suggested that the cytokine may affect cholesterol transport and/or availability to cytochrome P450scc in the mitochondria. Specifically, we report here that TNFalpha reduced in a dose- and time-dependent manner hCG-induced StAR (steroidogenic acute regulatory protein) levels. The maximal and half-maximal effects were obtained with 20 ng/ml (1.2 nM) and 1.6 ng/ml (0.09 nM) of TNFalpha, respectively. Maximal inhibitory effects of TNFalpha on StAR messenger RNA and protein levels were obtained after 48 h of treatment. Additionally, the presence of TNFalpha receptors P55 in terms of protein (identified through cross-linking experiments) and messenger RNA (identified through RT-PCR analysis) suggested that the effects of the cytokine are directly exerted on the testicular steroidogenic cell type.

Animals↗
PubMed1992

Interleukin-1 alpha as a potent inhibitor of gonadotropin action in porcine Leydig cells: site(s) of action.

The effects of interleukin on testicular steroidogenesis have been studied in several laboratories, most often by using cultured rat Leydig cells. Several reports have indicated that interleukin-1 beta (IL-1 beta), but not interleukin-1 alpha (IL-1 alpha), exert a potent effect on gonadotropin action in rat Leydig cells. By using cultured porcine Leydig cells as a model, we found that IL-1 alpha (and to a lesser extent IL-1 beta), contrary to previous reports, is a potent inhibitor of LH/hCG steroidogenic action; and we further localized the steroidogenic biochemical step(s) affected by IL-1 alpha. IL-1 alpha inhibited hCG-induced testosterone secretion (about 67%) in a dose- and time-dependent manner. Half maximal and maximal effects were obtained with 4 U/ml (approximately 0.4 ng/ml, 0.3 x 10(-10) M) and 20 U/ml (approximately 2 ng/ml, 1.4 x 10(-10) M) of IL-1 alpha, respectively. The inhibitory effect of IL-1 alpha on gonadotropin action was detected at 6 h and was maximal after 24 h of treatment with the cytokine. The IL-1 alpha inhibitory effect was more potent than that of IL-1 beta: the maximal inhibitory effect of IL-1 beta was obtained with 400 U/ml. Subsequent investigations indicated that IL-1 alpha inhibited different biochemical steps involved in gonadotropin-induced testicular steroidogenesis. In this context, although IL-1 alpha appears to inhibit Leydig cell membrane functions (through a decrease in LH/hCG binding and gonadotropin-induced cAMP production), the antigonadotropin action of the cytokine is probably exerted predominantly at a step(s) located beyond cAMP formation.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1999

Effects of acute exposure to PCBs 126 and 153 on anterior pituitary and thyroid hormones and FSH isoforms in adult Sprague Dawley male rats.

3,3'4,4',5-Pentachlorobiphenyl (PCB 126) and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153) were administered to adult male rats in order to identify sensitive indicators of endocrine disruption. We tested the hypothesis that PCB exposure modifies follicle-stimulating hormone (FSH) pituitary isoforms, as well as the pituitary and serum concentrations of FSH, luteinizing hormone (LH), growth hormone, prolactin, and thyroid-stimulating hormone (TSH). Effects on serum levels of thyroxine (T4) and testosterone (T), and prostate androgen receptor content, were also tested. In one experiment, 5 groups of 8 rats each received two i.p. injections, one day apart, of either corn oil or 6.25, 25, 100 or 400 micrograms/kg/day of PCB 126. Decreases (p < 0.05) in the serum concentrations of T4 and LH started at doses of 25 and 100 micrograms/kg/day, respectively. Serum FSH concentrations were reduced (p = 0.07) in the highest dose group. In contrast, pituitary content of FSH and LH increased with PCB-126 doses (p = 0.004, p = 0.002, respectively). Despite changes in reproductive hormones, PCB-126 had no effect on the androgen receptor content of the prostate. The effect of PCB-126 was tested in the hemicastrated rat, and suggested adverse effects on testosterone secretion. To test the effects of PCB exposure on FSH pituitary isoforms, 4 groups of 10 male rats received two i.p. injections, one day apart, of either corn oil, PCB 153 (25 mg/kg/day), estradiol-17 beta (E2; 20 micrograms/kg/day), or PCB 126 (0.1 mg/kg/day). Serum T4 levels were higher (p < 0.01) in the E2 and PCB 153 groups, and slightly reduced in the PCB 126-treated groups, compared to controls. Simultaneous purification of pituitary FSH and TSH isoforms was performed by HPLC, using two chromatofocusing columns in series. In contrast to TSH isoforms, the distribution of FSH isoforms over the chromatography run differed slightly between treatment groups; the amounts of FSH isoform eluted during the pH gradient were lower (p < 0.05) in E2 and PCB 153-treated rats than in control or PCB 126-treated rats. The similarity between the effects of E2 and PCB 153 on T4 and FSH isoforms supports the contention that PCB 153 possesses estrogenic properties. Serum LH and T4 concentrations were the most sensitive and practical endocrine indicators of PCBs 126 and 153 exposure in male rats.

Animals↗
PubMed1988

Luteotropic activity in serum of women following embryo or gamete transfer in a program of assisted conception.

In an attempt to track the proliferation/demise of trophoblastic tissues in women following gamete transfer (GT) or in vitro fertilization/embryo transfer (IVF/ET), we have measured levels of human chorionic gonadotropin (hCG) in serum of 180 patients on days 7 and 14 following oocyte pickup (OPU). Serum hCG levels were measured by immunoassay and by a bioassay based on the capacity of the sample to stimulate testosterone secretion by cultured mouse Leydig cells. Based on determinations of bioactive and immunoactive hCG in serum from 18 of 180 patients who subsequently delivered (12 of 73 GT, 6 of 107 IVF/ET; P less than 0.05) and classification of patients in accord with their compliance or noncompliance with these ranges of values, about 70% of all patients in the present study were classified as "pregnant" 7 days following OPU. Based on these same criteria, about 23% were pregnant 7 days later. Biochemical pregnancy rates on days 7 and 14 following GT (near 73 and 27%, respectively) were not different from the respective values following IVF/ET (near 68 and 20%, respectively; P greater than 0.05). The luteotropin bioassay described is highly sensitive to hCG (to 0.02 mIU/ml serum) and appears appropriate to the characterization of proliferation/demise of embryonic tissues during the 14 days after gamete/embryo transfer. In addition, through its representation of the cumulative luteotropic properties of human serum and its insensitivity to biologically inactive hCG subunits, this bioassay appears more appropriate than hCG immunoassay in the monitoring of early embryonic signalling following assisted (or spontaneous) conception in the woman.

Chorionic Gonadotropin↗
PubMed1994

True hermaphroditism: genetic variants and clinical management.

The diagnosis and management of 22 patients with true hermaphroditism are described. Sixteen of them were first seen before the age of 4 months. The initial manifestations were ambiguous genitalia in 20 cases (two of them identified prenatally by ultrasound examination), isolated clitoromegaly in one, and penile hypospadias plus unilateral cryptorchidism in one. All patients but one had at least one palpable gonad. Eleven of the twelve patients examined before the age of 6 months had basal plasma testosterone levels > 0.4 ng/ml. In older patients the stimulation test was necessary to demonstrate male testosterone secretion. The most common peripheral karyotype was 46,XX (17 cases); the other karyotypes were 47,XXY (1 case) and mosaicism 46,XX/46,XY (2 cases) or 46,XX/47,XXY (2 cases). One of the patients with the 46,XX karyotype had 46,XX/46,XY on fibroblast culture; four had the SRY gene in their leukocytes and one in the tissue taken at gonadal biopsy. A vagina was found in all patients at laparotomy, and a uterus was found in 17 cases (as a hemiuterus in 9). Genitography failed to demonstrate a uterus in only one case. The testicular tissue was dysgenetic but the ovarian tissue was normal. Sex assignment was male in 8 patients (reoriented by us in 2) and female in 14 patients (reoriented by us in 3). Spontaneous pubertal development occurred in the 4 patients (2 boys, 2 girls) with gonadal tissue who reached pubertal age. We conclude that true hermaphroditism is a heterogeneous condition in terms of its genetic background, with a prevalence of the 46,XX karyotype. There may be mosaicism with a Y-bearing cell line limited to the gonad (its frequency is probably underestimated), a paternal meiotic exchange between X and Y occurring in 46,XX cases with SRY, or a lack of the SRY gene, suggesting that other genes working independently of SRY may also determine testicular differentiation.

Child↗
PubMed2001

Diagnosis and localization of testosterone-producing ovarian tumors: imaging or biochemical evaluation.

OBJECTIVE: In the testosterone-secreting ovarian tumor (TSOT), the role of whole-body positron emission tomography (WBPET) with (fluorine-18)-2-deoxyglucose scanning (FDG) and/or [(11)C]acetate is unclear, although it presents a rationale that these functional tumors would be more active and have increased use of glucose and oxygen consumption than normal tissues. CASE: A 52-year-old woman had a history of steroid cell tumors of the right ovary (IIA) and she received staging surgery including total hysterectomy, salpingo-oophorectomy, and lymph node sampling. Reelevated serum levels of T (5.24 ng/ml) were noted 52 months later. The patient received serial preoperative examinations including WBPET with FDG and acetate, ultrasound, computerized tomography (CT), and magnetic resonance imaging (MRI) to evaluate her recurrence. A suspicious mass on the liver was found on ultrasound, CT, and MRI. The ultrasound-guided biopsy was performed three times, and each of them failed to provide any pathological confirmation. Functional imaging studies showed an abnormal uptake in WBPET using [(11)C]acetate but were negative using FDG. Because of the size of the tumor, the patient's hesitatancy toward an operation, and good previous response to gonadotropin-releasing hormone (GnRH) agonist treatment, the patient received a six-cycle GnRH agonist treatment. Serum T levels returned to normal limits after administration of the first dose of GnRH agonist. At follow-up, serum hormone levels were all within the normal ranges consistent with menopause, but the size of the metastatic tumor was constant. The tumor was then completely excised pathologically proven to be a metastatic TSOT. CONCLUSIONS: Recurrent TSOT might be successfully detected using WBPET with [(11)C]acetate. In addition, GnRH agonist could be tried in patients with TSOT if initial responses were excellent and surgical intervention could not be performed.

Carbon Radioisotopes↗
PubMed2001

Nongenomic effect of testosterone on chloride secretion in cultured rat efferent duct epithelia.

Short-circuit current (I(sc)) technique was used to investigate the role of testosterone in the regulation of chloride secretion in cultured rat efferent duct epithelia. Among the steroids tested, only testosterone, and to a lesser extent, 5alpha-dihydrotestosterone (5alpha-DHT), reduced the basal and forskolin-induced I(sc) in cultured rat efferent duct epithelia when added to the apical bathing solution. Indomethacin, a 3alpha-hydroxysteroid dehydrogenase, did not affect the inhibitory effect of 5alpha-DHT. The effect of testosterone occurred within 10-20 s upon application and was dose dependent with apparent IC(50) value of 1 microM. The effect was abolished by removal of Cl(-) but not HCO from the normal Krebs-Henseleit solution, suggesting that testosterone mainly inhibited Cl(-) secretion. The efferent duct was found to be most sensitive to testosterone, while the caput and the cauda epididymidis were only mildly sensitive. Cyproterone acetate, a steroidal antiandrogen, or flutamide, a nonsteroidal antiandrogen, did not block the effect of testosterone on the forskolin-induced I(sc), nor did protein synthesis inhibitors, cycloheximide, or actinomycin D. However, pertussis toxin, a G(i) protein inhibitor, attenuated the inhibition of forskolin-induced I(sc) by testosterone. Testosterone caused a dose-dependent inhibition of forskolin-induced rise in cAMP in efferent duct cells. It is suggested that the rapid effect of testosterone was mediated through a membrane receptor that is negatively coupled to adenylate cyclase via G(i) protein. The role of nongenomic action of testosterone in the regulation of electrolyte and fluid transport in the efferent duct is discussed.

1-Methyl-3-isobutylxanthine↗
PubMed1997

Binding of rat and ovine epididymis-specific prealbumins (PES) to rat spermatozoa without effect of heterologous immunization on rat fertility.

The epididymis, under control of testosterone, secretes proteins which bind to the membrane of the spermatozoa during their passage through the lumen. One such class is termed PES (prealbumin epididymal specific). Injection of heterologous oPES (ovine PES) into male rats caused antibody production but failed to induce sterility, unlike results previously obtained when rat PES was injected into male rats. This suggests that only very restricted species-specific epitopes of PES might be useful for causing immunocontraception. Despite this, the sperm binding properties of PES purified from the rat (rat PES) and from the ram (oPES) were shown to be similar. When either rat PES or oPES, conjugated with a fluorescent probe (dimethylamino-fluorescein), was incubated with washed rat spermatozoa originating from the caput, corpus or cauda epididymis, results of flow cytometric analysis showed: (1) the number of spermatozoa bound to isologous or heterologous fluorescent PES, and (2) the binding-affinity of spermatozoa for PES was greater for sperm collected from more distal sites in the epididymis.

Animals↗
PubMed1983

A morphometric analysis of rat ventral prostate in organ culture.

A stereologic, morphometric method was used for determining the quantitative and qualitative changes in the rat ventral prostate during organ culture. The volume density of epithelium (VVEP), lumina (VVLU), and interstitium (VVIT) as well as the proportion of epithelium of the tissue, VVEP/(VVEP + VVIT), the length density of tubular structures (LV), mean diameter of the lumina (DLU), height of the epithelium (h), and mean width of the interacinar tissue (lambda AP) were evaluated. In the perfusion-fixed prostate these parameters gave the closest approximation for the in vivo situation: VVEP was 0.19 mm3/mm3; h 19.5 micron; VVEP/(VVEP + VVIT) 0.63 mm3/mm3; VVLU 0.70 mm3/mm3; DLU 230 micron; VVIT 0.11 mm3/mm3; lambda AP 84.1 micron; and LV 17.5 mm/mm3. Dissection of the prostate for culture caused leakage of prostatic secretions and a consequent diminution of VVLU (0.41 mm3/mm3) and DLU (151 micron), as well as folding of the epithelium and distortion of the interacinar tissue (VVIT 0.25 mm3/mm3). During 10 days culture in a defined medium, the prostate underwent involutive changes including loss of total weight, a decrease of VVEP, and an increase of VVIT. During the first day a stimulatory effect on the epithelium occurred, which might have been caused by a loss of androgenic control or by substances in leaking secretions. Testosterone postponed many of these changes and maintained the secretory function better. Thus, on day 4 the morphology of the prostate resembled better the situation in vivo than at the beginning of involutionary culture. However, later during culture changes, similar to those found without testosterone but weaker, were noted. Statistical analysis of data showed that it is more advisable to use many pieces from one prostate lobe rather than to use many animals. Analysis of one slice is also sufficient to give relevant data on that piece.

Animals↗
PubMedDate not supplied

Testicular blood flow in young and old rats and influence of hCG.

To evaluate the influence of age, testicular capillary blood flow (TCBF) was measured, using the microsphere technique, in rats 3 to 24 months old, under basal conditions and after hCG stimulation (10 IU/d for two days). Despite a decline in plasma T levels, testicular capillary blood flow did not decrease with age, and hCG stimulation resulted in similar increases of approximately 50% (P less than 0.01) in testicular capillary blood flow in all age groups. We concluded that the age-associated decrease in testosterone secretion in rats is not the consequence of a decreased testicular blood flow.

Aging↗
PubMedDate not supplied

Peptidergic innervation of blood vessels and interstitial cells in the testis of the cat.

We studied the innervation of the cat testis using a panel of antisera against the following neuronal markers: protein gene product 9.5 (PGP), neuropeptide Y, C-terminal peptide of neuropeptide Y, galanin, vasoactive intestinal peptide (VIP), calcitonin gene-related peptide, and substance P. Immunoreactivity against PGP, a general neuronal label, demonstrated the arrangement of fibers from the superior spermatic nerve (SSN) in the testicular pedicle and the cephalic testicular pole, and those of the inferior spermatic nerve (ISN) along the vas deferens and the inferior testicular ligament. The testicular parenchyma exhibited a very rich innervation, mainly distributed to blood vessels and Leydig cell nests, but also in close association with seminiferous tubules. Numerous peptidergic fibers were present in the SSN and ISN, albeit in different proportions. Thus, VIP-immunoreactive fibers were almost absent in the SSN, but were the most abundant subpopulation of the ISN. The testicular interstitium contained numerous peptidergic fibers, associated with blood vessels, interstitial Leydig cells, and seminiferous tubules. Similar fibers were related to the rete testis. Parenchymatous VIP-immunoreactive nerves disappeared after bilateral vasectomy. Stimulation of the ISN under experimental conditions was associated with an increase of blood flow, and induced a large release of VIP into the spermatic vein. The extensive and selective distribution of nerve fibers within the cat testicular parenchyma supports the importance of spermatic nerves for testicular function. Furthermore, the differences in the fiber composition of the SSN and ISN can be correlated with their opposing effects on testosterone secretion and testicular blood flow.

Animals↗
PubMed2002

Progesterone attenuates the inhibitory effects of cardiotonic digitalis on pregnenolone production in rat luteal cells.

Previous studies have shown that digoxin decreases testosterone secretion in testicular interstitial cells. However, the effect of digoxin on progesterone secretion in luteal cells is unclear. Progesterone is known as an endogenous digoxin-like hormone (EDLH). This study investigates how digitalis affected progesterone production and whether progesterone antagonized the effects of digitalis. Digoxin or digitoxin, but not ouabain, decreased the basal and human chorionic gonadotropin (hCG)-stimulated progesterone secretion as well as the activity of cytochrome P450 side chain cleavage enzyme (P450scc) in luteal cells. 8-Br-cAMP and forskolin did not affect the reduction. Neither the amount of P450scc, the amount of steroidogenic acute regulatory (StAR) protein, nor the activity of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) was affected by digoxin or digitoxin. Moreover, in testicular interstitial and luteal cells, progesterone partially attenuated the reduction of pregnenolone by digoxin or digitoxin and the progesterone antagonist, RU486, blocked this attenuation. These new findings indicated that (1) digoxin or digitoxin inhibited pregnenolone production by decreasing the activity of P450scc enzyme, but not Na(+)-K(+)-ATPase, resulting in a decrease on progesterone secretion in rat luteal cells, and (2) the inhibitory effect on pregnenolone production by digoxin or digitoxin was reversed partially by progesterone. In conclusion, digoxin or digitoxin decreased progesterone production via the inhibition of pregnenolone by decreasing P450scc activity. Progesterone, an EDLH, could antagonize the effects of digoxin or digitoxin in luteal cells.

17-Hydroxysteroid Dehydrogenases↗
PubMed1981

[Puberty].

Puberty commences in girls 1.5-2 years earlier than in boys. Whereas the production of sexual hormone in the female increases gradually, testosterone secretion in the male rises steeply within two years. In connection with this boys are suffering more often from emotional disturbances than girls during puberty. During the last 150 years the onset of puberty has considerably advanced. In the middle of the last century, menarche occurred at age 17; today, however, at age 12.5. This secular acceleration is caused by improved nutrition, mainly with proteins. Presupposition for the earlier onset of puberty is an earlier arriving at the developmental stage (height, weight, bone maturation) which formerly was characteristic for prepubertal children of 10/11 years. Also the physiologic variants, i.e., the so-called early normal puberty and constitutional delay of growth and adolescence, base on prepubertal differences in growth velocity and growth hormone secretion. In contrast to this, the pathologic variants of sexual development, i.e., true sexual precocity and pubertas tarda s.s., are caused by various pathologic processes located in one of the three areas: hypothalamus, pituitary, or gonads.

Adolescent↗
PubMed2003

A study of short utrophin isoforms in mice deficient for full-length utrophin.

Utrophin can functionally replace dystrophin in dystrophin-deficient muscle and may have a role in a therapeutic strategy for Duchenne muscular dystrophy. This has resulted in many investigations of the full-length muscle form of utrophin; however, the short utrophins and non-muscle forms have been relatively neglected, partly because they are difficult to analyze in the presence of the full-length form. Our study circumvents this problem by using mice deficient for the full-length form (UKOex6 mice) to study the translation and distribution of short utrophins. Four tissues were examined-kidney, testis, fetal hands/feet, and brain-and three novel short isoforms were identified, including Up120, which appears to be specific to kidney glomeruli, and Up 109, expressed in the fetal dermis. A third form, Up103, was found in testis but at extremely low levels. A cDNA for Up109 has been isolated and shown to have a unique NH2-terminal sequence. In addition, the first exons of Up109 and another short form, G-utrophin, have both been located within intron 55, 56 kb apart. Our immunological studies show that G-utrophin protein accumulates only in neural tissue, in line with its similarly restricted RNA distribution. Our study of testis expression shows, for the first time, that full-length utrophin is expressed at high levels in Leydig cells, raising the possibility that this protein is involved in testosterone secretion. We note that translation of the short utrophins, especially Up140 and Up71, is relatively inefficient and discuss the significance of this observation.

Amino Acid Sequence↗