Novel ring chromosome composed of X- and Y-derived material in a girl with manifestations of Ullrich-Turner syndrome.

We present a female infant who has a novel genetic variant of Ullrich-Turner syndrome. Chromosome analysis on amniotic fluid cells obtained because of ultrasound observation of nuchal thickening showed 45,X in all cells. The infant was born with a low posterior hairline and moderate edema over hands and feet. Postnatal chromosome analysis demonstrated two cell lines-47% of the metaphases were 45,X, but 53% had a ring chromosome in addition to the normal X. FISH studies using alpha satellite probes, an X-whole-chromosome-paint (WCP) probe, and a Y-cocktail probe determined that the ring was composed of both X and Y sequences. FISH studies also determined that the KAL locus was present on the ring, but that XIST was absent. PCR-based analysis of lymphocyte DNA documented that the ring contained sequences from both the short and the long arm of the Y chromosome. X-chromosome analysis using a panel of highly polymorphic markers indicated that the ring contained material derived only from Xp22.1 to Xp21.3. No Xq material was identified on the ring, and androgen receptor-based X-inactivation studies suggested that the intact X chromosome was not subject to random X inactivation.

Concentration of dihydrotestosterone and 3 alpha-androstanediol in naturally occurring and androgen-induced prostatic hyperplasia in the dog.

Previous studies have suggested that dihydrotestosterone accumulation in the prostate may be involved in the pathogenesis of prostatic hyperplasia in man and dog. However, the fact that the administration of 10 mg dihydrotestosterone/d to castrated, mongrel dogs (0.5 mg/kg body wt) causes little growth in the prostate, whereas identical doses of 3alpha- androstanediol regularly induce prostatic hyperplasia (> 14 g weight) has raised the possibility that the dihydrotestosterone accumulation may be the result rather than the cause of the pathology. To investigate the mechanism of this phenomenon, we measured the levels of dihydrotestosterone and 3alpha-androstanediol in prostates from 75 dogs. In both naturally occurring and 3alpha-androstanediol-induced prostatic hyperplasia, the levels of dihydrotestosterone were high (>5 ng/g), whereas in immature glands and glands from dihydrotestosterone-treated animals, levels were similar (2.1 and 2.6 ng/g, respectively). 3alpha-Androstanediol levels were no different in animals treated with dihydrotestosterone or 3alpha-androstanediol.Therefore, because exogenous 3alpha-androstanediol is a better precursor of prostatic dihydrotestosterone than exogenous dihydrotestosterone itself, the effects of treatment with larger doses (2.5 mg/kg per d) of dihydrotestosterone and 3alpha-androstanediol for 12 wk were examined. In these amounts, dihydrotestosterone was as effective as 3alpha-androstanediol in inducing the development of prostatic hyperplasia and in elevating prostatic dihydrotestosterone concentration. Because dihydrotestosterone accumulates in spontaneous prostatic hyperplasia, because the administration of sufficient amounts of dihydrotestosterone to the castrated dog can induce the development of prostatic hyperplasia, and because 3alpha-androstanediol induces the development of hyperplasia via conversion to dihydrotestosterone, we conclude that accumulation of dihydrotestosterone is the cause of canine prostatic hyperplasia.

Regulation of cytoplasmic dihydrotestosterone binding in dog prostate by 17 beta-estradiol.

17 beta-estradiol enchances androgen-induced prostate growth in the castrate dog to a degree comparable to that seen in spontaneous prostatic hypertrophy. To investigate the mechanism of this synergism, cytosol androgen binding was measured by a density gradient technique in prostates of control and 17 beta-estradiol-treated castrate dogs. [3H]Dihydrotestosterone was bound principally to a moiety that averaged 8.6S in size. Approximately twofold enhancement of this binding by 17 beta-estradiol was demonstrable after 1 wk of treatment with 750 microgram/wk and after 3 wk with 75 microgram/wk. Under conditions in which binding in the 8S region was demonstrable with dihydrotestosterone and testosterone no binding of 3 alpha-androstanediol or progesterone was detectable. Thus, enhancement by 17 beta-estradiol of a prostate cytosol androgen-binding protein occurs under circumstances in which 17 beta-estradiol enhances androgen-mediated prostatic growth.

Androgen insensitivity as a cause of infertility in otherwise normal men.

To ascertain if androgen insensitivity causes severe oligospermia or azoospermia we studied three unrelated, phenotypically normal men with long histories of infertility. The mean plasma concentrations and production rates of testosterone were 14.3 ng per milliliter and 10.1 mg per day, respectively, values approximately twice the average found in normal men. Serum luteinizing hormone concentrations were elevated in two of the three subjects. The specific high-affinity dihydrotestosterone binding capacity of cultured genital-skin fibroblasts was 8, 0 and 10 fmol per milligram of cellular protein, values half (or less) of those from normal men and women but similar to values in subjects with partial androgen insensitivity manifested by incomplete testicular feminization or Reifenstein syndrome. The low amount of androgen receptor and the combination of high serum gonadotropins and plasma testosterone production rates suggest that the defective spermatogenesis in these infertile men was the consequence of androgen insensitivity.