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PubMed1991

[True hermaphrodite with ipsilateral vas deferens and intrascrotal ovary].

A 15-year-old, legally male patient came to our department with chief complaint of gynecomastia. Serum testosterone was at a low level of 1.6 ng/ml, and prolactin a high level of 23 ng/ml. Blood type was a mixed type of both type A and type B, and a chromosomal analysis with peripheral blood lymphocytes demonstrated a mosaic of 46, XX/46, XY. During the follow-up, he complained a painful swelling in his right scrotum, and received an emergent surgery. A large amount of blood was noted in the right scrotum. Unicorn uterus, Fallopian tube and finbriae were observed, and a thumb-sized gonad with hemorrhage and fissure was also seen in the upper part of the scrotum. The right gonad was an ovary and no testicular tissue was confirmed in the right scrotum, whereas the right vas deferens was noted. The left testis was accompanied by an induration on its upper pole which was histologically found to be ovarian tissue. The patient was diagnosed as a true hermaphroditism with 46, XX/46, XY chimera that had an ovary with inguinal uterus hernia and an unusual vas deferens in the right scrotum and an ovotestis in the left. It was considered that an adequate amount of testosterone secreted from the left testis during the early embryonal period might have affected the descent of the right ovary into the scrotum and on the development of the right vas deferens.

Adolescent↗
PubMed2000

High incidence of receptors for luteinizing hormone-releasing hormone (LHRH) and LHRH receptor gene expression in human prostate cancers.

PURPOSE: Agonistic analogs of luteinizing hormone-releasing hormone (LHRH) are widely used for therapy of advanced prostate cancer based upon their ability to suppress testosterone secretion in patients. Various studies also indicate that LHRH analogs might have direct inhibitory effects on prostate tumors mediated by specific LHRH receptors. In this study we investigated the presence and characteristics of receptors for LHRH and their messenger (m) ribonucleic acid (RNA) expression in specimens of human prostate adenocarcinomas and benign prostatic tissue. MATERIALS AND METHODS: In vitro ligand competition assays as well as reverse transcriptase polymerase chain reaction (RT-PCR) were performed to investigate the expression of receptors for LHRH in surgical specimens of human prostate cancers and benign prostatic tissue. RESULTS: Sixty-nine of 80 (86%) cancers exhibited specific, medium to high-affinity binding for [D-Trp6]LHRH with a dissociation constant (Kd) of 6.55+/-0.4 nM and a maximal binding capacity (Bmax) of 483.6+/-25.4 fmol./mg. membrane protein. Two prostate cancer patients who were treated with the LHRH agonist goserelin prior to prostatectomy did not show tumor LHRH receptors. The expression of mRNA for LHRH receptors was observed in 19 of 22 (86%) prostate cancers. Benign prostatic tissue also displayed LHRH receptor gene expression, but exhibited lower Bmax value. There was a negative correlation (p <0.001) between LHRH receptor binding capacity and cancer grade (Gleason score); higher Gleason scores were associated with significantly lower binding capacity but an increased binding affinity. CONCLUSIONS: The expression of specific receptor proteins for LHRH in human prostate cancer provides a rationale for the improvement in methods for therapy of this malignancy based on LHRH analogs.

Aged↗
PubMedDate not supplied

Testicular pathology in 46,XY dysgenetic male pseudohermaphroditism: an approach to pathogenesis of testis cancer.

Eleven children with dysgenic male pseudohermaphroditism (DMP) and 18 boys with isolated penile hypospadias, all with 46,XY karyotype, were studied. Testicular dysgenesis was associated with significantly lower testosterone response to human chorionic gonadotropin (0.9 +/- 0.2 ng/mL) than it was in hypospadias (3.3 +/- 0.1 ng/mL), and with significantly higher mean serum follicle-stimulating hormone (FSH) levels (8.4 +/- 2.3 IU/L vs 1.5 +/- 0.3 IU/L). Gonadoblastoma, a tumor that arises from the sex cords, was found in more than 1/4 of patients with DMP, whereas testicular carcinoma in situ (CIS) cells were present in all of these patients. Forty-two percent to 98% of CIS cells revealed an aneuploid pattern of nuclear DNA, indicating that most of them are neoplastic cells. In patients with hypospadias, CIS was not seen, and no other abnormalities were detected. In children with DMP, the percentage of tubules populated with germ cells was significantly lower than it was in those with hypospadias (48.3% +/- 10.6% vs 92.4% +/- 4.0%). The total number of germ cells (CIS cells + spermatogonia) did not differ significantly between the 2 groups, but the number of spermatogonia was significantly reduced in children with DMP (0.08 +/- 0.05 vs 3.65 +/- 0.2), suggesting impaired differentiation of gonocytes to spermatogonia. The following significant correlations were present with DMP: 1) the higher the seminiferous tubule cross-section area, the higher the number of CIS cells (r = 0.78); and 2) the higher the serum gonadotropin levels, the higher were tubular diameter (r = 0.93 for FSH and r = 0.75 for luteinizing hormone [LH]), area (r = 0.79 for FSH and r = 0.82 for LH), percentage of tubules populated with germ cells (r = 0.86 for FSH and r = 0.81 for LH), and number of CIS cells (r = 0.87 for FSH and r = 0.79 for LH). The results indicate that in intersex children with 46,XY karyotype, CIS occurs in dysgenetic testes in all cases and is frequently associated with gonadoblastoma. Impaired organogenesis of sex cords, relative inhibition of testosterone secretion, and the associated increased secretion of gonadotropins may create a milieu that induces or is favorable for the formation or maintenance of neoplastic lesions in dysgenetic testes early in childhood.

Child↗
PubMed2002

Is aging a disease? A review of the Serono Symposia Workshop held under the auspices of the 3rd World Congress on the Aging Male. February 9, 2002, Berlin, Germany.

On February 9, 2002, Serono Symposia sponsored a workshop at The 3rd World Congress on The Aging Male that was held in Berlin, Germany at the Hotel Inter-Continental. The title of the workshop 'Is aging a disease?', was intended to convey recent interest in the subject of aging as a clinically relevant entity and to discuss causes and approaches to its management. The Workshop was co-chaired by Drs Viktor Büber and Richard F. Walker. Speakers included Drs George R. Merriam, Heinrich M. Schulte, Felice Strollo and Richard F. Walker. Topics were arranged to proceed from a general overview of fundamental aspects of the aging process and their clinical consequences to specific aspects of the diagnosis and treatment of age-related disorders that could be associated with neuroendocrine dysfunction. F. Strollo initiated the series of lectures by reviewing some of the biological theories of aging and suggesting that maladaptive changes within the central nervous and endocrine systems play a major role in contributing to the cascade of events defined as senescence. R. Walker expanded upon this background by differentiating aging and disease. He suggested that while the process of aging is not a disease, it is directly responsible for the development of functional decrements causal of the intrinsic disease, frailty and general morbidity that occur in direct relation to advancing chronological age. From this generalized approach of linking age and disease, G. Merriam discussed a specific example in which age-related decrements in neuroendocrine dysfunction could contribute, at least in part, to senescent changes in body composition and physiological function. Specifically, he provided evidence that the gradual decline in growth hormone (GH) and testosterone secretion during aging is accompanied by anatomical and functional changes resembling pathogenic hormone deficiency. He went on to discuss possible interventions into this process, specifically showing data to support the view that a combination of GH secretagogues and sex hormones may be of value in sustaining health and vitality in the elderly. As an extension of this discussion, H. M. Schulte compared and contrasted age changes in sex hormone secretion between genders, and also stressed that the diagnosis and management of endocrine changes during life has become a serious challenge to those physicians intending to intervene in the aging process. Because the relationship of reduced hormone secretion to disease in the elderly is presently unclear, the Workshop concluded on a note of caution that guidelines for the replacement of endocrine substances as a prophylactic approach to aging have yet to be defined.

Aged↗
PubMed2003

Gonadal function and pubertal development after treatment of a childhood malignancy.

As survival rates for childhood cancer have improved, the importance of assessing gonadal dysfunction caused by alkylating agents and radiotherapy in children treated for cancer has increased. Infertility is the major long-term side effect of chemotherapy (CT) in males, whereas Leydig cell function is less affected. Our studies confirm that prepuberty does not protect the male gonad from the late effects of CT and that protocols less gonadal-lesive (such as ABVD regimens) should be preferred. Ovaries are less affected, but early depletion of follicles and premature menopause may occur. High-dose busulfan conditioning regimens cause ovarian failure in young females. The role of gonadal irradiation is discussed: high dosages (>2000 cGy) provoke sterility, impaired testosterone secretion in males and estradiol release in females. High dosage hypothalamic-pituitary irradiation causes delayed puberty and hypogonadism in males and females, whereas lower dosages may be associated with early puberty, particularly in females.

Antineoplastic Agents↗
PubMed1992

[Various indicators of the hormonal profile in patients with neuroses after psychopharmacotherapy and functional test with sinacten].

Studies of adenohypophyseal hormones, cortisol, T3, T4, thyroxine-binding globulin, testosterone, progesterone and estradiol in 90 neurotic men, treated or not with amitriptyline and benzodiazepines, allowed a conclusion that in the majority of them, endocrine functions were activated. 11 healthy men and 11 male patients underwent the three-day test with sinacten-depot (1 mg intramuscularly). The functional test data were compared over time by the methods of nonparametric statistics. The patients manifested a decrease of reserve potentialities of the pituitary-adrenal system, redistribution of the fractions of thyroid hormones, gonadotropins, the progesterone/estradiol ratio, a rise of prolactin and testosterone secretion. The drugs were found to improve the functioning of the pituitary-adrenal system. However, they did not contribute much to the positive changes in the pituitary-thyroid and other systems.

Adrenal Cortex Hormones↗
PubMedDate not supplied

Dihydrotestosterone is a peripheral paracrine hormone.

Androgen action in sexual tissues, especially skin and the prostate, is expressed by dihydrotestosterone (DHT) acting at the nuclear level. Dihydrotestosterone in the circulation and target tissues is almost solely derived from the peripheral conversion of secreted testosterone (T) in men and androstenedione in women. The general pathway is testosterone----DHT in equilibrium with androstanediol (3 alpha diol). However, a number of studies suggest that blood DHT or 3 alpha diol are not reliable indicators of peripheral DHT formation. This is particularly suggested by discrepancies in the specific activity of DHT in blood and urine following infusion of labeled DHT, suggesting that total body DHT formation is not reflected by blood levels. Thus, DHT should be thought of as a paracrine hormone formed and acting primarily in target tissues. 3 alpha androstanediol glucuronide (3 alpha diol G) is a major metabolite of DHT. An important site of its formation is the skin. Levels in blood and urine are increased in hirsutism and acne, and blood levels closely parallel pubertal development. 3 alpha diol G levels are especially increased in adrenal disorders of androgenicity such as andrenogenital syndrome; it is also a good marker of response to therapy. Levels are reduced in various forms of male pseudohermaphroditism. 3 alpha androstanediol glucuronide appears to be the best marker available of DHT formation in target tissues such as skin.

Dihydrotestosterone↗
PubMed2006

The influence of polychlorinated biphenyls (PCBs) and phytoestrogens in vitro on functioning of reproductive tract in cow.

Ovarian, endometrial and myometrial cells and strips of longitudinal myometrium from cows on defined days of estrous cycle were treated for 24-72 h with different doses (1-100 ng/ml) of PCBs mixture (Aroclor 1248) or with one of PCB congeners (126, 77, 153). The administered doses of PCBs neither affected the viability of cells nor influenced the ovarian steroidogenesis as measured by progesterone (P(4)), estradiol (E(2)) and testosterone secretion from luteal, granulosa and theca cells, respectively. In contrast, PCBs clearly inhibited a FSH and LH-stimulated effect on steroids secretion from granulosa and luteal cells. Moreover, PCBs significantly stimulated oxytocin (OT) secretion from the studied ovarian cells, and at least part of this effect is elicited through activation of glucocorticoid receptors. Further, PCBs were found to increase basal intracellular concentrations of Ca(2+) and both spontaneous and OT-stimulated contractions of myometrial strips. Concomitantly, PCBs increased endometrial secretion of PGF(2alpha), hence the ratio of PGF(2alpha):PGE(2) was also increased. Phytoestrogens (genistein, daidzein, coumestrol), with a different intensity, reduced the effect of PCBs on PGF(2alpha) secretion and myometrial contractions. Genistein inhibited PCBs' effect on OT secretion from granulosa cells, while PCB's effect on OT release from luteal cells was reduced mainly by genistein and daidzein. We conclude that PCBs can impair both ovarian functioning and uterine contractility, while phytoestrogens are able to reduce this effect.

Animals↗
PubMed2006

[Alterations of gonadal axis and sexual steroids concentration in the conditions of intoxication with phenol in the experiments].

It is known that the male reproduction system is too sensitive to the impact of the environment conditions. One of such endocrine deregulators is phenol. The experiment was held on the 40 adult male albino rats of the mass 200-250 g. Each animal during 15 days was daily experienced intoxication with phenol in the special closed cabin. On the 16th, 30th, 45th and 60th days after the initiation of the experiment we performed decapitation of the animals in conditions of general anesthetic, after what in the blood serum we defined alteration of the concentration of gonadotrope hormones LH, FSH and sexual steroids--testosterone, estrone, estradiol, by means of immune-enzyme method. During the experiment the significant alterations of hormones concentration were revealed, namely, in the mentioned research it was revealed that LH did not stimulate the testosterone secretion, conversely it decreased, while the estrogen concentration increased. The mentioned data gave us basis to conclude that the impact of the phenol vapor caused disorder of the male reproduction function.

Animals↗
PubMed2006

[Expression and role of nitric oxide synthase in the testis and epididymis of Macaca fascicularis].

OBJECTIVE: To investigate the expression and the role of nitric oxide synthase (NOS) in the testis and epididymis of macaca fascicularis. METHODS: The immunohistochemical ABC method was used to observe the localization of nitric oxide synthase in the testis and epididymis of the macaca fascicularis. RESULTS: (1) nNOS immunoreactivity was found in the spermatogenic cells of seminiferous tubules, the epithelia of epididymal efferent ducts, sperm and the endothelia of blood vessels; (2) iNOS was expressed in the epididymal efferent duct, the sperm inside the duct, and the myoid cells and endothelia of blood vessels; (3) eNOS immunoreactivity was detected in the interstitial cells of the testis, the epididymal efferent duct, the sperm inside the duct, and the myoid cells and endothelia of blood vessels. CONCLUSION: NOS is extensively expressed in the testis and epididymis of the macaca fascicularis and it may play an important role in such processes as spermatogenesis, sperm maturation and testosterone secretion.

Animals↗
PubMed1991

Role of hypothalamic catecholamines in aging processes.

Defects that develop in the hypothalamic area of the brain are believed to initiate many declines in body functions in aging rats and mice. The decreases found in hypothalamic norepinephrine and dopamine are particularly important since they lead to reduced gonadotropic hormone secretin and cessation of estrous cycles in female rats and a decrease in testosterone secretion in male rats, lower GH and somatomedin (IGF-I) secretion and reduced protein synthesis, diminished thyroid hormone secretion and lower body metabolism, higher PRL secretion and development of numerous mammary and pituitary tumours, and reduced immune competence. The reduction in hypothalamic norepinephrine and dopamine activity is believed to be due to damage and loss of neurons owing to toxic products formed during metabolism of norepinephrine and dopamine; to the damaging effects to neurons produced by the chronic action of estrogen, PRL, and indirectly by adrenal glucocorticoids; and to changes in enzymes responsible for synthesis and metabolism of norepinephrine and dopamine. When old rats are given drugs that elevate norepinephrine and dopamine, most of the above and other decrements of aging are delayed or reversed, and length of lifespan may be prolonged. Decreases in hypothalamic norepinephrine and dopamine have also been reported in elderly human subjects, but it is unknown whether these are related to declines in body functions.

Aging↗
PubMedDate not supplied

Ontogeny of 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) in human testis as studied by immunocytochemistry.

The enzyme complex 3 beta-hydroxy-5-ene-steroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) is involved in the biosynthesis of all classes of active steroids, including androgens. To correlate possible changes in 3 beta-HSD with the well-known variations in testosterone secretion during development, the authors localized this enzyme by immunocytochemistry during fetal and postnatal periods of development in the human testis. In the fetal testis, 3 beta-HSD was detected in Leydig cells during the second and third trimester of gestation. In 8-month-old and 11-year-old boys, however, no immunoreaction could be detected in the testis. In pubertal boys, Leydig cells appeared well developed and immunopositive. Since the fluctuations in 3 beta-HSD immunoreactivity are similar to those already observed for androgen secretion, activation of 3 beta-HSD by trophic hormones may play an important role in androgen production during fetal and postnatal development.

Adolescent↗
PubMedDate not supplied

[The effect of prolactin and bromocriptine on testicular incretory function].

Prolactin (PRL) is synthesized by lactotropic pituitary cells. The corresponding hormonal preparations is dispensed as lactin. Bromocriptine is a dopamine agonist, dopamine being a natural inhibitor of PRL-secretion. PRL receptors in the testis are located on the interstitial cells. PRL effect on the testis depends on the age and species of animals. In the immature animals as well as in the photoperiodic ones PRL stimulates the testis development and the testicular secretion; bromocriptine decreases androgen concentration. In the postpubertal animals PRL is a melatonin antagonist in the dark time but LH synergist at the exposure to light. A high PRL concentration inhibits gonadoliberin formation, LH secretion; testosterone concentration and especially dihydrotestosterone concentration decrease (or do not change) with an elevation of estradiol level that on the whole results in feminization. The cerebral transmitters promoting or inhibiting sexual behavior are involved in the interaction with PRL. Administration of PRL, experimental or pathological hyperprolactinemia are followed by the suppression of ejaculation. Bromocriptine (parlodel) appears to be a pathogenetic therapeutic agent in hyperprolactinemia.

Aging↗
PubMed1987

Effects of zeranol on reproduction in beef bulls: scrotal circumference, serving ability, semen characteristics, and pathologic changes of the reproductive organs.

Effects of zeranol on scrotal circumference, serving ability, semen characteristics, and postmortem measurements of the genital organs were determined in beef bulls from 9 to 20 months of age. Group 1 (n = 5) served as a nonimplanted control group. Group 2A (n = 5) was implanted with 36 mg of zeranol at birth and at 3 and 6 months of age. Group 2B (n = 5) was implanted with 36 mg of zeranol every 3 months from birth through 18 months of age. Scrotal circumference was adversely affected by zeranol in groups 2A and 2B, but values approached those of group 1 with increasing age. Serving ability was also affected adversely but tended to recover with increasing age. Semen quality was low in groups 2A and 2B and did not improve with increasing age. There was no difference in testicular weight, vesicular gland weight, and penis length among groups when bulls were slaughtered at 20 months of age. Epididymal weight was greater in group-2B bulls and was most likely a consequence of epididymal lesions. Histologic examination of the genital organs revealed that zeranol induced adenomyosis and sperm granulomas in the caudae epididymidis and markedly altered the structure of the sexual accessory glands of bulls in groups 2A and 2B. Alterations in the vesicular glands were characterized by reduced alveolar development and an increase in connective tissue. Low epithelium associated with focal areas of squamous metaplasia were common in the prostate of groups 2A and 2B bulls. Lesions in the bulbourethral glands were characterized by low glandular epithelium, focal areas of squamous metaplasia, cystic collecting ducts, and an increase in connective tissue. Groups 2A and 2B had more abnormal seminiferous tubules than did group 1. Lesions in groups 2A and 2B may have been direct effects of zeranol or may have resulted from reduced testosterone secretion.

Animals↗
PubMed1978

The role of H-Y antigen in primary sex determination.

The basic embryonic plan of mammals is inherently feminine. Male development is due to two-step interventions of this basic plan: the Y chromosome directs the embryonic indifferent gonad to organize a testis instead of an ovary; the Y-organized testis synthesizes and secretes testosterone, which induces all the extragonadal masculine development. The Y chromosome plays no direct and appreciable role in extragonadal masculine development. Testicular organization, normally under the direction of the Y, is the function of the evolutionary conserved plasma membrane protein serologically detectable as H-Y antigen. Under specific circumstances, H-Y antigen may be expressed in the absence of the Y chromosome, thus producing XO and XX males. If H-Y antigen is not expressed, XY individuals develop as females. H-Y antigen is the first plasma membrane or cell surface protein to which a specific organogenesis function has been assigned.

Adolescent↗
PubMed1983

[Surgical indications in testicular ectopias].

The ideal age for treatment is still controversial. However, all recent histological studies show that the number of spermatogonia and the diameter of the tubules remain virtually normal until the beginning of the third year of life. Treatment therefore should take place in the second year, after all chances of spontaneous migration have vanished and before lesions due to cryptorchidism develop. Chorionic gonadotropic hormones should be used systematically; they avoid surgery in only one out of five cases, but they make it possible to test the possibilities of testicular descent and testosterone secretion. Surgical treatment should follow precise rules. The spermatic vessels might, if necessary, be severed, but care must be taken to preserve the gubernaculum. The alternative is, microsurgical autotransplantation. Only time will show whether the poor fertility of these patients is bettered by early treatment.

Cryptorchidism↗
PubMedDate not supplied

[Cryptorchidism: pathogenesis and histology].

An impairment of the hypothalamopituitarygonadal axis was found to be the main cause of undescended testicles in 80 per cent of patients. Basing himself on personal observation, the author develops the theory that the mechanism of testicular descent is the stimulation by GnRH of the pituitary gland to release gonadotrophins, which in turn stimulate the interstitial cells to secrete testosterone. High local testosterone concentration fosters the development of the differentiating portion of the mesonephric duct into the epididymis. The epididymis induces descent by pushing rather than pulling the testis into the scrotal position. Any interference with this mechanism during the embryonal life leads to cryptorchid testes, which, in the vast majority of cases are localized at the external inguinal ring. The earlier the scrotal position is reached, the greater the chances of subsequent fertility.

Cryptorchidism↗
PubMed1982

[Mechanism of androgenopoiesis disorder in stress].

Experiments on pubertal male rabbits were made to study the effect of prolonged stress (daily one-hour immobilization and electrocutaneous stimulation for a fortnight) on hormonal and structural gonadal function. The prolonged action of stress was shown to result in the drastically lowered testicular androgenopoiesis. Inhibition of testosterone secretion by the tests was not determined by structural disorders of the hormone-producing Leydig cells which were functionally activated under the conditions described. This activation appears to be related to the production of steroids that are not characteristic for the activity of the intact gonads.

Androgens↗