Modulation of free plasma zinc levels has been implicated in the increase in plasma prolactin levels seen in patients with chronic renal insufficiency (CRI). The relative importance of this mechanism in comparison to others, however, has not been elucidated. Zinc equilibrium between plasma and red blood cells is partly dependent upon red blood cell carbonic anhydrase (CA). In the present paper, we have investigated the interrelationships among total plasma zinc, leukocyte zinc, prolactin, and erythrocyte CA in patients with CRI. Uremic patients were shown to have significantly increased levels of plasma prolactin and erythrocyte CA activity when compared to normal controls. Moreover, red blood cell CA total concentration and isoenzyme-I and-II levels, as well as plasma zinc were found to be significantly decreased in uremic patients in comparison to normal controls. In patients with CRI, a negative correlation was demonstrated between erythrocyte CA catalytic activity and plasma zinc, as well as between plasma zinc and plasma prolactin levels. Moreover, leukocyte zinc content, which is a reliable indicator of total body zinc stores, was found to be significantly decreased in uremic patients when compared to normal controls. A strong negative correlation between leukocyte zinc content and plasma prolactin levels was documented in CRI patients. Our results suggest that alterations in erythrocyte CA levels, enzymatic activity or isoenzyme profile are most probably mechanistically and etiologically unrelated to the high plasma prolactin levels in CRI patients. Contrariwise, depletion of total body zinc stores, rather than redistribution of this trace metal among extracellular compartments, may represent one of the major contributing mechanisms leading to uremic hyperprolactinemia.

Adrenal glands from a patient with ACTH-independent Cushing's syndrome, whose symptoms worsened during pregnancy and oral contraceptive use, were cultured in different concentrations of estradiol. Estradiol stimulated cortisol secretion in a dose-response manner in the absence of ACTH. Since immunoglobulins G from this patient did not stimulate corticosterone production in a mouse adrenal bioassay, an adrenal-stimulating immunoglobulin is unlikely to be the cause of adrenal hyperfunction in this case. This is the first description of estradiol stimulation of cortisol production by cultured adrenal cells in ACTH-independent Cushing's syndrome.

Recent studies from our laboratory have shown that human chorionic gonadotropin (hCG), human luteinizing hormone (hLH), and CG-like proteins from Xanthomonas maltophilia (xCG) and Candida albicans (CaCGLP) induce Candida albicans transition from blastospores to hyphal forms. Xanthomonas maltophilia CG-like protein (xCG), hCG, and hLH also bind to Candida albicans blastospores with a high-affinity nM Kd, indicating that these substances can control Candida albicans pathogenicity. The work reported herein describes the purification of the binding site for these CG-like proteins from Candida albicans. The purification developed involved alcohol extraction followed by affinity chromatography. The product obtained was a protein of 64-69 kDa, as analyzed by sodium dodecyl sulfate-polyacrylamide electrophoresis (SDS-PAGE), Western blot and Sephadex G-100 column chromatography. This binding site reacted in a Western blot with both 125I-hCG and 125I-CaCGLP. Purified CaCGLP was able to displace specifically 125I-hCG bound to Candida albicans blastospores. Scatchard plot analysis showed that the Kd of this reaction was of high affinity in the nM range, and also indicated the presence of one single binding site. These results lead us to conclude: 1) Candida albicans possesses a binding site which is able to bind hCG, hLH and CG-like proteins from Xanthomonas maltophilia and Candida albicans; 2) This binding site is a hydrophobic protein of approximately 64 kDa and; 3) We postulate that CaCGLP is the natural ligand for this binding site and this system is used to control Candida albicans transition and, therefore, pathogenicity.

Candida albicans, a dimorphic fungus, is involved commonly in human infections with the mycelium form more associated with pathogenicity. The influence of various hormones and a bacterial protein on the transition from blastospore to mycelium was assessed. Human luteinizing hormone (hLH), chorionic gonadotrophin (hCG), and an hCG-like material purified from a bacteria, Xanthomonas maltophilia (PCG), were able to increase the rate of transition when compared with the controls. The effect of the two hormones and the bacterial peptide were specific, as human follicle stimulating hormone (hFSH), thyroid stimulating hormone (hTSH), growth hormone (hGH), prolactin (hPrl) and rat and bovine LH (rLH, bLH), and bovine albumin and gamma globulin did not affect the transition. The binding of 125I-hCG or 125I-LH to spheroplasts of Candida albicans were competitively displaced by hCG, hLH, and PCG. Scatchard analysis of binding of all three ligands revealed two binding sites with a high-affinity nM Kd. Thus, hCG, hLH, and PCG induce transition of Candida albicans from a blastospore state to a mycelium form, suggesting that these hormones may modify the pathogenicity of Candida albicans.

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