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Treatment of purified rat ovarian plasma membranes with N,N'-dicyclohexylcarbodiimide (DCC) abolishes the subsequent response of adenylate cyclase [EC 4.6.1.1, ATP pyrophosphate lyase (cyclizing)] to lutropin (LH) and follitropin (FSH) but not to NaF. Such treatment also inhibits binding to these membranes of iodinated [125I] human chorionic gonadotropin (125I-hCG). Preincubation for 30 min at room temperature with 70 microM DCC reduces the response of adenylate cyclase to LH by 50% whereas 4 times higher concentration is required to reduce 125I-hCG binding to the same extent. At 0.5 mM, DCC reduces both activities by 50% within 8-10 min. Preincubation of the membranes with hCG prior to treatment with DCC protects the hormone-binding site of the receptor but not the ability of the enzyme to respond to LH. Thus the enzyme becomes functionally uncoupled. It is suggested that at least two distinct sites in the enzyme system are affected by DCC. Both sites are located proximal to the regulatory step that involves GTP-binding protein. One site seems to be associated with the receptor and the second is located distal to receptor-hormone complex formation.

The etiology of diabetes in some conditions of iron overload is not known. We studied growth, glucose tolerance, and pancreatic islet cell morphology and cytochemistry in rats administered parenteral FeNTA. These rats developed glucosuria, slowing of growth with eventual weight loss, polyuria, polydipsia, and death. They had normal fasting plasma glucose levels but decreased glucose tolerance and insulin response to glucose. Although no Prussian blue staining of iron was observed in pancreatic islets by light microscopy, at the ultrastructural level insulin-secreting beta-cells showed ferrin iron deposits localized to the plasmalemma and the cytoplasmic surface of secretory granule membranes. Prussian blue staining was also observed in parenchymal cells of the liver, heart, and kidney, in order of decreasing intensity. Animals treated with an equivalent dose of NTA, saline, or iron-dextran in saline had normal growth and response to glucose and did not exhibit pancreatic iron deposits at the light or ultrastructural level. These results support the hypothesis that iron affects pancreatic islet cell function and may be an etiologic agent of diabetes mellitus in hemochromatosis.

The hypothesis has been advanced that the two genes on chromosome 6 determining idiopathic hemochromatosis are not identical alleles and therefore that the disease is not recessively inherited, but rather that two different genes are involved. A study of 63 families points to: (a) the rarity with which a single hemochromatosis gene finds biochemical expression (in only 1 of 5 cases), as revealed through determinations of serum iron, serum ferritin and the desferrioxamine test; (b) no difference in HLA-antigen marking between genes with and those without biochemical expression: (c) no difference other than that produced by chance in the biochemical expression of the two genes in families; and (d) the finding in one highly informative family of identical expression of the two genes. It is concluded that idiopathic hemochromatosis is determined by two homologous alleles in accordance with the classical mode of recessive inheritance.

The dextran-coated charcoal assay method of McGuire and DeLaGarza is a well-known method for quantitation of oestrogen receptors in breast tumour tissues. Castañeda and Liao reported that the solid-phase antisteroid antibodies are superior to dextran-coated charcoal for quantitating the receptor bound steroids. In this report we compare the results obtained using both methods to quantitate oestrogen receptors and determine the affinity for steroid binding in seven human breast tumours and the uteri of rat and calf.