A B S T R A C T Influences of estrogen and progesterone on the development of hyperinsulinemia and augmented pancreatic islet insulin secretion during pregnancy were assessed in this study. Groups of female rats were injected subcutaneously for 21 days with varying daily dosages of estradiol benzoate or progesterone in oil. On day 21, pancreatic islets were isolated by a collagenase method. Total insulin secretion was measured after 90-min incubations of 10 islets in buffered medium containing glucose. Higher physiologic dosages of estradiol or progesterone, singly or in combination, significantly increased islet secretion above values of untreated control rats and were comparable to augmented islet responses of term, 3-wk pregnant rats. Diameter and protein content of islets obtained from steroid-treated and pregnant rats exceeded control measurements in these instances. However, 2-hr preincubations of control islets with 1 or 10 /g/ml of either steroid did not influence subsequent glucose-stimulated insulin output.In related studies, plasma insulin responses during 30 min intravenous glucose tolerance tests were significantly above control responses in term-pregnant rats and animals receiving comparable dosages of steroids for 3 wk. Unlike pregnancy or progesterone treatment, estradiol administration alone or with progesterone significantly lowered postchallenge plasma glucose concentrations.Dr. Costrini was a pre-doctoral student in the Department of Physiology when these studies were performed. He is currently a sophomore medical student in a combined M.D. These results indicate that estradiol and progesterone contribute to enhanced islet insulin secretion and plasma insulin responses to glucose administration during pregnancy. This change is not acutely produced but can be related to hypertrophy of islets following chronic hormonal administration. Although the data do not distinguish between direct and indirect beta-cytotrophic effects of these sex steroids, metabolic actions of estradiol and progesterone may differ, since estrogen treatment lowers plasma glucose curves following the induction of hyperinsulinemia.

A B S T R A C T Plasma insulin dynamics were evaluated in 10 patients with primary hyperparathyroidism before and after parathyroidectomy and correction of hypercalcemia. Before surgery fasting plasma insulin concentrations and insulin responses to administered glucose, tolbutamide, and glucagon were significantly greater than postoperative values. Hyperinsulinemia was not associated with altered glucose curves during glucose or glucagon tolerance tests, but a relatively greater insulin response to tolbutamide resulted in an increased hypoglycemic effect following its administration. The glucose-lowering action of intravenous insulin was slightly impaired before treatment. Intramuscular injections of parathormone to six normal men for 8 days induced mild hypercalcemia and hypophosphatemia and reproduced augmented plasma insulin responses to oral glucose and intravenous tolbutamide. 4-hr intravenous infusions of calcium to another group of six normal men raised serum calcium concentrations above 11 mg/100 ml. This did not alter glucose or insulin curves during oral glucose tolerance but markedly accentuated insulin responses to tolbutamide and potentiated its hypoglycemic effect. When highly purified parathormone was incubated with isolated pancreatic islets of male rats, glucose-stimulated insulin secretion was unaffected.These findings suggest that chronic hypercalcemia of hyperparathyroidism sustains a form of endogenous insulin resistance that necessitates augmented insulin secretion to maintain plasma glucose homeostasis. This state is insufficient to oppose tolbutamide-induced hypoglycemia because of an additional direct, selective en-

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Nerve growth factor (NGF), a hormone-like regulator of sympathetic neuron ontogeny and metabolism, affects its target cells initially by associating with specific plasma membrane receptors. We have solubilized the NGF receptor of adult rabbit superior cervical ganglia (SCG) with the nonionic detergent Triton X-100. The high-affinity equilibrium binding constant of the detergent-extracted receptor is 2-8 X 10-10 M. Gel chromatography of the receptor or the 125I-labeled NGF-receptor complex on a column of Sepharose 6B indicated, in both cases, a single component of an apparent hydrodynamic radius of 71 ± 5 A. In parallel investigations, we have confirmed the similarity between the hydrodynamic size of the NGF receptor of rabbit SCG and that of the insulin receptor of IM-9 lymphocytes evaluated by similar methods. Nerve growth factor (NGF) is a hormone-like polypeptide that is responsible for the growth, development, and maintenance of the sympathetic nervous system. As with other substances of related function, it appears that the first step is the association of the factor with a specific recognition site (receptor) on the surface of responsive cells (1). The binding characteristics of this receptor from both sympathetic and sensory neurons have been extensively studied (2-4) and Banerjee et al. (5) have shown that the NGF receptor can be extracted from the cell surface by nonionic detergents without loss of its ligand binding activity. In this report we present the binding characteristics and apparent molecular size of the NGF receptor extracted from rabbit superior cervical ganglia (SCG) with the nonionic detergent Triton X-100. MATERIALS AND METHODSPreparation of NGF and 125I-Labeled NGF (1251-NGF). 2.5S NGF was prepared from mouse submaxillary glands according to the method of Bocchini and Angeletti (6). 125I-NGF was prepared by a modification (5) of the Bolton and Hunter (7) technique. A mixture of 5 mCi (1 Ci = 3.7 X 101 becquerels) of 12'I-labeled Bolton-Hunter reagent (New England Nuclear; specific activity, 1500 Ci/mmol) and 1 nmol of 2.5S NGF in 10-20 1.l of ice-cold 0.1 M borate pH 8.5 buffer was allowed to react for 10 min. Then the reaction was stopped with 100 1.l of 0.5 M glycine in borate buffer. Iodinated NGF was separated from other components of the reaction mixture by chromatography on Sephadex G-25 (fine; 1 X 16 cm). 125I-NGF was 95-98% trichloroacetic acid-precipitable and 90-95% immunoprecipitable. Incorporation of labeled reagent varied from 20 to 40%; specific activities varied from 900 to 2000 cpm/fmol ,uCi/,ug; up to 0.5 mol of reagent per mol of NGF). Higher specific activities could be obtained by increasing the reaction time; however, this was attended by damage to the NGF as judged by higher nonspecific binding in the radioreceptor assay.The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact.In order to minimize backgro...

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