Central hypogonadism: distinguishing idiopathic low testosterone from pituitary tumors.

Objective: To attempt to determine clinical or hormonal characteristics that could help distinguish benign idiopathic low testosterone (ILT) from pituitary tumor.

Methods: On retrospective review of medical records of patients encountered by Johns Hopkins endocrine staff between 1985 and July 1995, 64 patients who fulfilled our enrollment criteria--27 men with ILT and 37 patients with imaging-proven pituitary tumor--were identified. Men 21 years of age or older needed to have had serum testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin levels measured before hormonal replacement therapy or pituitary tumor extirpation (or both) and a high-quality imaging scan (computed tomography or magnetic resonance imaging) done and interpreted by the Johns Hopkins radiology staff.

Family history of alcoholism and hypothalamic opioidergic activity.

Background: This study was designed to assess whether nonalcoholic offspring from families with a high density of alcohol-dependent individuals have altered endogenous central nervous system opioid activity. Naloxone hydrochloride stimulates plasma cortisol by blocking opioidergic input on the corticotropin-releasing factor neuron, thereby providing a noninvasive method for measuring hypothalamic opioid tone.

Methods: Forty-eight nonalcoholic subjects aged 18 to 25 years were enrolled in a protocol to measure endogenous opioid activity by inducing opioid receptor blockade with the receptor antagonist, naloxone.

Assessment of adrenal function in women heterozygous for adrenoleukodystrophy.

Adrenoleukodystrophy (ALD) is an X-linked recessive disorder that destroys the white matter of the brain and is associated with adrenal insufficiency. The prevalence of adrenal dysfunction in 71 women carriers of the X-linked ALD gene was studied. These subjects were identified initially on the basis of being obligate carriers of the X-linked trait by pedigree analysis and were confirmed by plasma very long chain fatty acid levels consistent with a heterozygote status.

Comparison of steroidogenic potencies of homologous and heterologous gonadotropins in rat and mouse Leydig cells.

The in vitro steroidogenic potencies have been determined in rat and mouse Leydig cells for two homologous human gonadotropins, lutropin (hLH) and choriogonadotropin (hCG), and two heterologous gonadotropins, hCG beta wild-type and the product of an hCG beta clone containing a premature termination codon at position 122, each associated with a co-expressed bovine alpha subunit. hCG was found to be more potent than hLH in rat, but not mouse Leydig cells, and the heterologous gonadotropin containing the truncated hCG beta subunit was equipotent to that with hCG beta wild-type in both rat and mouse Leydig cells. Persistent steroidogenesis was determined by measuring testosterone production following pre-incubation with each of the above four gonadotropins and with ovine LH, subsequent washing of the cells, and re-incubation in the absence and presence of additional hormone.

Site-directed mutagenesis of the human chorionic gonadotropin beta-subunit: bioactivity of a heterologous hormone, bovine alpha-human des-(122-145)beta.

Human CG contains an alpha-subunit, common to the pituitary glycoprotein hormones, and a hormone-specific beta-subunit, but unlike the pituitary beta-subunits, hCG beta is characterized by an O-glycosylated carboxy-terminal extension. A mutant beta-subunit, des-(122-145)hCG beta, was prepared using site-directed mutagenesis, and the pRSV expression plasmids were transfected into Chinese hamster ovary cells that produce the bovine alpha-subunit (b alpha). The mutant beta-subunit binds to b alpha, and the heterologous gonadotropin, b alpha-des-(122-145)hCG beta, was capable of stimulating steroidogenesis in cultured Leydig tumor cells (MA-10) to the same extent as standard hCG.