Renin can be detected in cardiovascular and other tissues but it disappears after bilateral nephrectomy indicating that tissues can take up or bind renal renin from the circulation. If renin uptake is the result of specific binding, plasma prorenin may be a natural antagonist of tissue directed renin-angiotensin systems. To investigate if specific prorenin/renin uptake occurs in rat tissues, binding studies were performed, with rat microsomal membrane preparations using recombinant rat prorenin metabolically labeled with 35S-methionine as a probe. A high affinity binding site for both renin and prorenin was identified. Affinities for prorenin and renin were approximately 200 and 900 pmol/L, respectively. Binding was reversible, saturable, and pH and temperature dependent. The relative binding capacities of membranes from various rat tissues were as follows (fmol/mg): renal cortex (55), liver (54), testis (63), lung (31), brain (18), renal medulla (15), adrenal (17), aorta (7), heart (4), and skeletal muscle (1). Bound prorenin was displaced by rat and human renin or prorenin but not by the prosequence of rat prorenin, angiotensin I or II, rat or human angiotensinogen, the renin inhibitor SQ30697, atrial natriuretic factor, amylase, insulin, bovine serum albumin, hemoglobin, heparin, lysozyme, ovalbumin, cytochrome C, pepsin, pepsinogen, ribonuclease A, mannose-6-phosphate, alpha-methyl mannoside, gonadotropin releasing hormone, or an antibody to hog renin binding protein. these results demonstrate specific binding of prorenin to a site in rat tissues, herein named ProBP, that also binds renin. It is possible that differences in prorenin/renin binding capacity determine the activity of tissue-directed renin-angiotensin systems and that prorenin is a natural antagonist. Alternatively, a prorenin/renin receptor may have been identified that may function by transducing an intracellular signal.

A thyroid hormone antagonist has not been previously described. A number of thyroid hormone analogues have been shown to compete with ["25Iltriiodothyronine (1125I1T3) for bind-ing to the intranuclear thyroid hormone receptor and to have agonist activity proportional to their affinities for the receptors. We report that the benzofuran amiodarone acts as a competitive antagonist to thyroid hormone action as defined by its dose-dependent ability to (a) bind to the thyroid hormone receptor and (b) inhibit T3-induced increases in growth hormone mRNA levels in a cultured rat pituitary cell line, GC cells. Like T3 itself, amiodarone also decreases transport of 112511T3 across GC cell membranes. An analysis of the amiodarone structure suggests that this compound has certain similarities to T3. These findings hold promise for the development of other thyroid hormone antagonists for clinical use and for understanding thyroid hormone action.

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New procedures for the rapid purification and covalent labeling of the (3-adrenergic receptors have been developed that should greatly accelerate progress in the study of these widely distributed adenylate cyclase-coupled receptors. Chromatography of solubilized receptor preparations on a Sepharosealprenolol affinity gel followed by HPLC on steric exclusion columns lead to rapid (2 days) and high yield ("-

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Thyroid hormones have an in uence on the connectivedermal blood ow as a consequence of increased metatissue biology of the skin and, theoretically, topically bolic rate and decreased systemic vascular resistance applied thyroid hormones or hormone analogues could have and are thus not attributable to a direct action of TH a stimulatory eVect on collagen synthesis. In this investion cells in the skin (2-5). However, it is also known gation the eVect of topical tri-iodothyroaceti c acid (Triac) that the connective tissue biology of the skin is sensitive and other thyroid hormone analogues were tested for their to alterations in thyroid hormone status (3) and the eVect in preventing betamethasone-indu ced skin atrophy in presence of intracellular receptors ( TRs) for thyroid the normal haired mouse. Triac, tri-iodoproprioni c acid hormones in human skin, in both dermal and epidermal ( Triprop) and the synthetically developed thyroid hormone parts, have been demonstrate d (6-10). analogue KB-026 and 2 diVerent Triac cream formulationsInformation concerning the mechanism of action of TH were applied along with betamethasone on shaved mouse in broblasts, especially in regulation of collagen producskin. Triac in daily doses of 1 nmol/cm2 and higher was tion, is limited. In one study by Rycker et al., thyroid able to block the betamethasone-induce d skin atrophy in hormone administration diminished collagen production mice skin. In high doses, Triprop and KB-026 also had a in cultured broblasts (9). Although a vast number of blocking eVect. Triac alone had a stimulatory eVect on studies on thyroid hormone action in organs such as liver, dermal thickness. This study indicates that thyroid hormone heart, pituitary, brain and adipose tissue have been peranalogues may be used to prevent corticosteroid-induce d formed, no studies have been undertaken to investigate skin atrophy. Keywords: animal model; skin thickness; the activity of topical TH in glucocorticoid-treated skin. normal haired mouse.Moreover, as TRs are part of a larger superfamily of nuclear receptors, which comprises the receptors for gluco-

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