The etiology of certain disorders of sexual differentiation is unclear. The authors have examined the hypothesis that hypospadias and other disorders compatible with a defect in androgen action, such as cryptorchidism, micropenis, chordee/penile torsion, and ectopic testis, might be explained by androgen receptor abnormalities. Therefore, 25 subjects were studied who were selected only because they had one of these developmental defects, together with a predominantly male phenotype, and no readily ascertainable explanation for the defect. Four of these subjects had mixed gonadal dysgenesis with multiple genito-urinary anomalies. They were included for comparative purposes, since there is no evidence for androgen resistance in this disorder. Patients with testicular regression syndrome (gross testosterone deficiency), impaired testosterone biosynthesis (relative testosterone deficiency), 5 alpha-reductase deficiency (altered T/DHT ratio), and a family history or endocrine profile suggestive of androgen resistance, were all excluded from evaluation. Androgen receptor content (R0) and binding affinity (Kd) were measured in 26 genital or pubic skin fibroblast strains cultured from 25 affected patients using a dispersed, whole cell assay at 22 C. There was no difference in the mean androgen receptor content (approximately 10,000 sites/cell) or binding affinity (approximately 1 nM) between the patients' fibroblasts and those from 26 fibroblast strains established from 26 normal males. Moreover, there were no differences in the nuclear uptake of [3H]dihydro-testosterone into dispersed, intact fibroblasts incubated at 37 C when 11 patient and seven normal male fibroblast strains were compared.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMedDate not supplied

Predominant involvement of mu-rather than delta- or kappa-opiate receptors in LH secretion.

Opiate alkaloids and opioid peptides have been shown to suppress plasma LH and FSH levels via a naloxone sensitive mechanism in several species including man. Three subtypes of opiate receptors have been characterized: mu, delta and kappa. The present study was designed to investigate their role in gonadotropin release. Three highly selective opioid ligands, DAGO, MRZ and DTE12 (a dimeric tetrapeptide enkephalin), were injected intraventricularly into chronically ovariectomized rats. Injection of the mu-agonist at doses of 1 and 10 nmol produced a significant suppression of LH secretion, while the delta- and kappa-agonists had no significant effect. Thus, the mu-receptor seems to be the primary opiate receptor involved in the regulation of LH secretion. None of the opiate agonists employed had an effect on FSH secretion.

Animals↗

PubMedDate not supplied

Localization of GRF-like immunoreactive neurons in the rat brain.

The localization of human GRF1-44-immunoreactive neurons was studied in the rat brain. A dense accumulation of GRF-containing fibers was noted in the external layer of the median eminence. Cell bodies were observed in colchicine-treated rats. The most intensely fluorescent cluster of cells was contained in the arcuate nucleus. Other cells were seen on the base of the hypothalamus, within the median forebrain bundle, dorsal and ventral aspects of the ventromedial nucleus, zona incerta and dorsal part of the dorsomedial nucleus. These cells may influence the pulsatile release of pituitary growth hormone.

Animals↗

PubMedDate not supplied

Hemodynamic effects of corticotropin releasing hormone in the anesthetized cynomolgus monkey.

Right atrial bolus administration of rat/human corticotropin releasing hormone (r/hCRH) at a dose of 90 micrograms/kg to anesthetized cynomolgus monkeys caused a dramatic and prolonged fall in both the peripheral vascular resistance (48% reduction) and mean systemic blood pressure (36% reduction). An associated tachycardia could be blocked with prior propranolol administration and thus was probably reflexic. A mean 43 and 37% increase in the flow of the superior mesenteric and common iliac arteries, respectively, was demonstrated with electromagnetic flow probes. These changes were associated with a concomitant 38 and 40% diminution in the respective vascular resistance. Similar blood flow changes were noted in the carotid artery, however, these were of a much shorter duration. None of these changes occurred in placebo-treated animals. Plasma adrenocorticotropic hormone and cortisol concentrations were elevated basally and throughout the procedure and were similar in the experimental and control groups, suggesting maximal activity of the hypothalamic-pituitary-adrenal axis. Plasma renin activity, however, gradually increased in the r/hCRH-treated animals, probably as a result of the systemic hypotension. We speculate that CRH or a CRH-like substance may function as a paracrine hormone modulating local blood vessel tone and may be important in directing blood flow during stress and injury. The vasoactive properties of exogenous r/hCRH may be of clinical use in man.

Animals↗

PubMedDate not supplied

Resistance to multiple steroids in two sisters.

A 14-year-old Native American girl from the Iroquois Nation was referred as a potential patient with the syndrome of Apparent Mineralocorticoid Excess. Instead, her evaluation revealed resistance to glucocorticoids, mineralocorticoids, and androgens. She lacked Cushingoid features in spite of significantly high cortisol levels. Menstruation was regular and there was no clinical evidence of masculinization despite high serum androgen levels in the male range. The patient's sister had similar clinical features. Partial resistance to exogenous glucocorticoid and mineralocorticoid administration was well demonstrated in both patients. It is proposed that these patients represent the first cases of partial resistance to multiple steroids, possibly owing to a coactivator defect.

Adolescent↗

PubMedDate not supplied

Gadolinium DTPA enhanced MR imaging of ACTH-secreting microadenomas of the pituitary gland.

Gadolinium diethylenetriamine pentaacetic acid (DTPA) enhanced magnetic resonance imaging was performed in eight patients with Cushing disease and surgically proven pituitary microadenomas. A 1.5 T scanner was used with 3 mm contiguous slices. Short repetition times (TR), short echo times (TE), and long TR, long TE sequences were obtained before and serially after intravenous administration of Gd-DTPA. Three of eight (38%) microadenomas were undetectable both without and with Gd-DTPA: one post-Gd-DTPA scan was false positive on the side opposite the adenoma. Hemihypophysectomy based on a petrosal sinus adrenocorticotropic hormone (ACTH) gradient cured all three patients. Two microadenomas (25%) were visible as hypointense foci following Gd-DTPA but not on unenhanced scans. The remaining three microadenomas (38%) were seen before and after Gd-DTPA on T1-weighted images. In this small series of ACTH-producing microadenomas, one-third were seen on unenhanced 1.5 T scans, one-third were seen only after Gd-DTPA, and one-third were not imaged even with Gd-DTPA enhancement.

Adenoma↗

PubMedDate not supplied

The effects of testosterone on plasma and platelet monoamine oxidase (MAO) an plasma dopamine-beta-hydroxylase (DBH) activities in the male rhesus monkey.

Dopamine-beta-hydroxylase (DBH) and monoamine oxidase (MAO) in plasma and platelets were studied in male rhesus monkeys to evaluate the effects of changes in endogenous testosterone on the activity of these enzymes. High plasma testosterone concentrations attained at the end of the mating season were associated with relatively low levels of platelet MAO activity. When testosterone levels fell, platelet MAO increased significantly. Mean differences in platelet MAO activity between a group of castrated and control males were in the direction expected, with the highest MAO activity in the castrated monkeys, but these differences did not attain statistical significance. No significant mating season or castration effects were seen in plasma DBH or MAO enzyme activities. These data support the hypothesis of a link between testosterone and some monoamine systems, and possibly the monoamine-related behaviors linked to testosterone in primates.

Animals↗

PubMedDate not supplied

Late-onset 21-hydroxylase deficiency is an allelic variant of congenital adrenal hyperplasia characterized by attenuated clinical expression and different HLA haplotype associations.

Three families with late-onset 21-hydroxylase deficiency were studied. Homozygous females presented with symptoms of mild hyperandrogenism such as acne, hirsutism, oligomenorrhea and menometrorrhagia. A homozygous male was asymptomatic and had reached normal adult height. The diagnosis of 21-hydroxylase deficiency was based upon markedly elevated responses of plasma 17-hydroxyprogesterone during a short (30-min) ACTH infusion test. The propositi of two of the families were diagnosed despite long-standing glucocorticoid therapy and adrenal suppression by using a prolonged (48-hour) ACTH infusion. Heterozygotes of late-onset 21-hydroxylase deficiency had mildly elevated 17-hydroxy-progesterone responses to ACTH. Late-onset 21-hydroxylase deficiency was inherited as an autosomal recessive trait with close linkage to the histocompatibility leukocyte antigens. The B14 haplotype was present in all affected members. One affected female had a daughter with classic, salt-losing 21-hydroxylase deficiency. Mixed heterozygosity of this patient for a classic and a late-onset 21-hydroxylase deficiency allele may have caused the classic phenotype in her daughter (homozygote for 2 classic alleles).

Adrenal Hyperplasia, Congenital↗