Molecular analysis of ring y chromosome in a 10-year-old boy with mixed gonadal dysgenesis and growth hormone deficiency.

Ring Y chromosome is a very rare chromosomal aberration. The published mixed gonadal dysgenesis (MGD) patients with a ring Y chromosome are short in stature, but are not growth hormone (GH) deficient. We present the molecular cytogenetic and molecular characterization of ring Y chromosome mosaicism in a 10-year-old boy with MGD whose short stature could be explained by the high percentage of cells monosomic for the X-chromosome, but also by the presence of severe GH deficiency. The ring Y chromosome in our patient is a de novo structural aberration. The father's karyotype was normal.

Effect of diazepam on plasma corticosterone levels.

In light of the numerous but rather conflicting reports on the action of benzodiazepines upon the hypothalamo-hypophyseal-adrenal (HHA) axis activity, the effect of different doses of diazepam (0.1, 1.0 and 10.0 mg/kg) administered 15, 30, 60, 120 and 240 min before decapitation on plasma corticosterone level was studied in rats. While 0.1 mg/kg diazepam had no effect, 1.0 mg/kg diazepam decreased plasma corticosterone levels 30 and 60 min following drug administration. On the other hand, treatment with 10.0 mg/kg diazepam produced an increase in plasma corticosterone levels from 15-120 min following drug administration.

Effect of diazepam on brain neurotransmitters, plasma corticosterone, and the immune system of stressed rats.

Rats were treated with injections of diazepam (1 or 10 mg/kg) and stressed by restraint lasting 3 hours. This was performed once or, in animals immunized with sheep erythrocytes, repeatedly for 4 consecutive days. After repeated stress and/or diazepam treatment, the levels of brain noradrenalin decreased in all treated groups. Although both treatments (stress and diazepam) diminished the 5-hydroxytryptamine (5-HT)/5-hydroxyindoleacetic acid (5-HIAA) ratio, treatment with either dose of diazepam prevented the stress-induced fall of this ratio. The activity of hypothalamic glutamate decarboxylase, the enzyme taking part in GABA synthesis, was affected neither by the acute nor by repeated stress and/or diazepam treatment. The levels of plasma corticosterone were enhanced in all stressed rats, with and without drug. This finding was in accordance with the enhanced weights of adrenal glands in repeatedly stressed rats. The tendency to a corticosterone rise after repeated treatment with diazepam, 10 mg/kg, coincided with the enhanced weights of adrenal glands in these animals. The plaque-forming cell (PFC) response was reduced in all stressed animals and in animals treated with diazepam, 10 mg/kg. Accordingly, high doses of diazepam given repeatedly to rats are immunosuppressive, achieving this effect presumably by an enhancement of glucocorticoid secretion. Neither the low nor the high doses of diazepam affect the stress-induced enhancement of hypothalamohypophysial-adrenal axis activity and consecutive immunosuppression.

Sex differences in the response of rats to drugs affecting GABAergic transmission.

The administration of diazepam 1.0 mg/kg decreased the level of plasma corticosterone in female but not in male Wistar rats. Picrotoxin, another drug affecting GABAergic transmission, also brought about an increase of plasma corticosterone in both sexes. However, in order to achieve a plasma corticosterone increase of similar magnitude (more than 500%) a threefold higher dose of picrotoxin had to be given to males. When the convulsive properties of picrotoxin were tested, it became evident that the dose of picrotoxin (2.5 mg/kg) which was subconvulsive in male was almost 100% convulsive in female rats. The existing sex differences in the response of rats to drugs affecting GABAergic transmission might have possible implications in the treatment of GABA system dysfunction.

Mechanisms by which picrotoxin and a high dose of diazepam elevate plasma corticosterone level.

Picrotoxin (1 mg/kg, i.p.) and a high dose of diazepam (10 mg/kg, i.p.) increased the concentration of plasma corticosterone in nonstressed rats. This effect of diazepam was unaffected by picrotoxin and bicuculline (GABA-A receptor blockers), atropine (a muscarinic receptor blocker), apomorphine (a dopamine receptor agonist), haloperidol (a dopamine receptor blocker) and yohimbine (an alpha-2-adrenergic receptor blocker); but was blocked by clonidine (an alpha-2-receptor agonist) and this effect of clonidine was reversed by yohimbine. Diazepam was unable to elevate plasma corticosterone levels in rats pretreated with dexamethasone. Clonidine and the GABA-B receptor agonist, baclofen, failed to affect the picrotoxin-induced rise of plasma corticosterone, but this rise was abolished by a low dose of diazepam (1 mg/kg). The results suggest that the diazepam-induced enhancement of ACTH release, presumably mediated by blockade of alpha-2-adrenergic receptors, is responsible for the observed increase of plasma corticosterone level in rats. On the other hand, the elevation of plasma corticosterone induced by picrotoxin appears to be mediated by GABA-A receptors.