Feminization, altered gonadal development, and liver damage in least killifish (Heterandria formosa) exposed to sublethal concentrations of 17α-ethinylestradiol.

The widespread use of the synthetic estrogen 17 α-ethinylestradiol (EE2) has resulted in elevated levels in aquatic environments, where it is known to act as an endocrine disrupting chemical affecting fish and other aquatic organisms. Examining changes in the structure of the fish' gonads and liver has proven to be an effective approach for assessing these impacts. While changes have been reported for various fish species, it is not clear whether impacts are equally severe in live-bearing fishes. The present study looked at gonadal and liver development in EE2-exposed least killifish (Heterandria formosa), a live-bearing Poeciliid. Exposures to 0, 5, or 25 ng/L EE2 began within six days of birth and continued until fish became sexually mature 12-23 weeks later. Exposure to 5 ng/L EE2 resulted in severe intersex in fish with external male characteristics, a slowdown of spermatogenesis in these intersex fish and a slowdown of oogenesis in the female fish. Moreover, these fish had a variety of liver injuries. Fish exposed to 25 ng/L EE2 exhibited intersex but at a lower frequency than occurred at 5 ng/L. In contrast, liver damage and slowdown of both oogenesis and spermatogenesis exhibited the typical dose-dependence. These findings illustrate the importance of including histological analyses when assessing endocrine disruption in fish, demonstrate that the live-bearing mode of reproduction appears to provide limited protection from the effects of waterborne EE2, and provide further evidence that EE2 has multiple impacts on fish health and reproduction that are severe enough to potentially affect fish populations.

SRY-positive 46, XY male with vanishing testis syndrome, feminization and gynecomastia.

The vanishing testis with maleness is a rare syndrome with frequency of 1 in 20,000 males. Here, we report about a 30 years old male subject with vanishing testis syndrome, feminization and gynecomastia. Follicle stimulating hormone (FSH) and Leutinizing hormone (LH) levels were elevated whereas testosterone was below normal and anti-mullerian-hormone level was undetectable in the patient. The chromosomal analysis and DNA analysis of SRY and ZFY, DAX-I, AZFa, AZFb, AZFc and heterochromatic region of Y chromosome with STS primer (sY160) were done to detect any genetic changes at specified sites (both at chromosomal and molecular level). Karyotyping confirmed patient as 46, XY male, with no evidence of mosaicism in blood cells. PCR amplification of SRY gene indicated that the SRY gene of the patient was normal. PCR amplification of SRY, ZFY, DAX-I, AZFa, AZFb, AZFc gene and Y chromosome heterochromatic region using STS primer sY(160) did not reveal any microdeletions. The anti-mullerian-hormone level was undetectable indicating that the patient didn't have any testicular tissue in scrotum. Increased levels of FSH, LH and reversed androgen: estrogen ratio might have given rise to gynecomastia in the patient. SRY-positive 46,XY male with vanishing testis might be due to torsion of testis during descent in fetal period. The torsion of testis might have caused vascular occlusion and thereby regression of testicular tissue occurred, but the exact genetic condition yet to understand.

Feminizing adrenocortical carcinoma with selective suppression of follicle-stimulating hormone secretion and disorganized steroidogenesis: a case report and literature review.

We report a 61-year-old male with gynecomastia, poor libido and erectile dysfunction. Endocrinological studies showed high levels of estradiol and dehydroepiandrosterone sulfate. Although luteinizing hormone (LH) level was within the normal limit, the concentration of follicle-stimulating hormone (FSH) was under the normal limit. Delayed response of LH and poor response of FSH to gonadotropin-releasing hormone administration were detected. Magnetic resonance imaging of the abdomen revealed a left adrenal tumor. Although the surgically-resected tumor was diagnosed as a high grade ACC based on Weiss's criteria of adrenocortical malignancy, no metastasis was detected. Since estrogen levels normalized after resection, feminizing ACC was confirmed. While LH concentration increased slightly after operation, FSH level became transiently elevated over the normal limit, and finally reached the normal range. These data may suggest that FSH was suppressed selectively by hormone produced by ACC different from estrogen.

Persistent Mullerian duct syndrome in a Miniature Schnauzer dog with signs of feminization and a Sertoli cell tumour.

A 5-year-old male Miniature Schnauzer was presented with unilateral cryptorchidism and signs of feminization. Abdominal ultrasonography revealed an enlarged right testis and a large, fluid-filled cavity that appeared to arise from the prostate. Computed tomography revealed the cavity to be consistent with an enlarged uterine body, arising from the prostate, and showed two structures resembling uterine horns that terminated close to the adjacent testes. The dog had a normal male karyotype, 78 XY. Gonadohysterectomy was performed and both the surgical and the histological findings confirmed the presence of a uterus in this male animal, resulting in a diagnosis of persistent Mullerian duct syndrome (PMDS). The enlarged intra-abdominal testis contained a Sertoli cell tumour. Computed tomography proved to be an excellent diagnostic tool for PMDS.

[Modern concepts in the treatment of intersexuality]. / Zum aktuellen Stand der Intersextherapie.

Treatment of intersexuality is demanding and requires experience and interdisciplinary cooperation. Preconditions for normal development and clear gender identification are correct (not emergency) diagnosis and gender assignment and adequate hormonal and surgical treatment. Surgery should be done early (6th to 15th month) as atraumatically as possible with cosmetically and functionally satisfying results. These preconditions are not met consistently, resulting in a 20-25% rate of mistakes in diagnosis and treatment. In experienced centers, feminizing genitoplasty, even of the severest forms, is carried out through a perineal one-stage approach. Masculinization corresponds to surgery for severe hypospadias. The high risk of malignant degeneration requires removal of all inadequate structures such as streak gonads, uterus, and tubes. In 5-alpha deficiency, early gonadectomy and feminization are not recommended since gyneophile behavior can be expected. Late or non-correction is rejected by the majority of psychiatrists. Many problems remain unclear and controversial due to lack of knowledge. In the future they can only be solved through cooperation, documentation, and observation of these individuals over their lifetime.

Disorders of pubertal development: precocious puberty.

Puberty is a complex developmental process culminating in sexual maturity. This transitional period begins in late childhood and is characterized by maturation of the hypothalamic-pituitary-gonadal axis, the appearance of secondary sexual characteristics, acceleration of growth, and, ultimately, the capacity for fertility. Significant endocrinologic changes accompany these developmental events. Disorders of pubertal development may occur at any of the steps of the maturational process leading to either precocious or delayed puberty. A thorough understanding of the normal pubertal process is important to the accurate diagnosis and treatment of pubertal disorders.

Hypogonadism is not related to the etiology of liver cirrhosis.

We investigated the clinical and laboratory findings of hypogonadism and feminization in male patients with viral or alcoholic cirrhosis to determine whether chronic liver disease plays a primary role in the development of sexual dysfunction and hormonal changes. Two groups of male patients with liver cirrhosis (23 alcoholic, 33 viral) age- and Child's grade-matched, and 20 age-matched healthy men, as a control group, were included in this study. Clinical signs of hypogonadism and feminization were examined in the cirrhotic patients. Follicle-stimulating hormone, luteinizing hormone, prolactin, testosterone, free testosterone, estradiol, androstenedione, dehydroepiandrosterone sulfate, and sex hormone-binding globulin were estimated in all groups. Seminal fluid was also analyzed in 7 alcoholic and 15 viral cirrhotics. Serum levels of estradiol, androstenedione, and sex hormone-binding globulin were significantly higher, and free testosterone and dehydroepiandrosterone sulfate levels were significantly lower in both groups of cirrhotics compared with the control group. Child's C patients in both groups of cirrhotics were found to have higher estradiol and lower free testosterone levels than child's A and B patients. Alcoholic and viral cirrhotics had markedly reduced sperm motility and density. The differences between alcoholic and viral cirrhotic patients in the clinical signs of hypogonadism, serum levels of sex steroids, and the results of seminal fluid analysis were not statistically significant. These findings suggest that liver cirrhosis per se, independent of etiology, causes hypogonadism and feminization, and that the degree of hypogonadism and feminization correlates well with the severity of liver failure.

Molecular genetics of androgen insensitivity syndromes.

The androgen receptor belongs to the family of nuclear receptors and contains three functional domains: a carboxy-terminal hormone binding region, a central cystein rich DNA binding region and an amino-terminal region involved in the expression of androgen regulated genes. Cloning of the complementary DNA encoding the androgen receptor enabled the characterization of the molecular defects associated with androgen insensitivity syndromes, X-linked disorders resulting from androgen action defects in target cells. Moreover, androgen receptor gene alterations have been recently described in two unrelated diseases: male breast cancer and spinal and bulbar muscular atrophy. Our group have identified 16 androgen receptor gene alterations in patients with androgen insensitivity syndrome, an amino acid substitution in a patient with a partial androgen insensitivity syndrome and a breast cancer. In 2 families, the molecular diagnosis of spinal and bulbar muscular atrophy has been performed.

[Tumors of the adrenal glands in children]. / Opukholi nadpochechnykh zhelez u detei.

The article presents results of diagnostics and treatment of 26 children with tumors of the adrenals. The diversity of clinical symptoms was dependent on the zone of the adrenal cortex where the adrenocortical tumors were developing and the character of the hormones released. In diagnostics of the localization of adrenal tumors the authors give preference to pneumoretroperitoneography. A conclusion is made that the hormonal background must be studied in each patient with gynecomastia and pneumoretroperitoneography should be performed. Such a watchfulness is thought to be the only condition of the timely diagnostics of esteroma.

Adrenal imaging.

The problems inherent in visualizing the adrenal glands are illustrated by the variety of imaging modalities that have been employed. Although urography has been the basic screening examination, one can make a sound argument for CT as the procedure of choice in the evaluation of the patient with suspected adrenal pathology. Angiography, venous sampling, and radionuclide studies continue to have a role in selected problem cases. This article reviews the usefulness of available modalities in the context of the clinical evaluation of adrenal disease.

A report on three cases of feminising syndrome in the dog.

Three cases of feminising syndrome are described in the male dog. All cases showed similar symptoms, alopecia being the most noticeable. Differential diagnosis is discussed. The beneficial effect of castration is recorded.

Bone marrow hypoplasia in eight dogs with Sertoli cell tumor.

Eight male dogs with Sertoli cell tumor had pancytopenia and bone marrow hypoplasia attributed to endogenous estrogen myelotoxicosis. Clinical signs were hemorrhage caused by thrombocytopenia, anemia caused by blood loss or diminished erythrocyte production, and infection and fever associated with granulocytopenia. Other signs attributed to hyperestrogenism were feminization and prostatic disease. Two dogs recovered after castration and supportive treatment, but 5 other similarly treated dogs died of hematopoietic failure. One dog was euthanatized.