We have deduced the entire 1,370-amino-acid sequence of the human insulin receptor precursor from a single complementary DNA clone. The precursor starts with a 27-amino-acid signal sequence, followed by the receptor alpha-subunit, a precursor processing enzyme cleavage site, then the beta-subunit containing a single 23-amino-acid transmembrane sequence. There are sequence homologies to human epidermal growth factor receptor and the members of the src family of oncogene products.

To identify structural characteristics of the closely related cell surface receptors for insulin and IGF‐I that define their distinct physiological roles, we determined the complete primary structure of the human IGF‐I receptor from cloned cDNA. The deduced sequence predicts a 1367 amino acid receptor precursor, including a 30‐residue signal peptide, which is removed during translocation of the nascent polypeptide chain. The 1337 residue, unmodified proreceptor polypeptide has a predicted Mr of 151,869, which compares with the 180,000 Mr IGF‐I receptor precursor. In analogy with the 152,784 Mr insulin receptor precursor, cleavage of the Arg‐Lys‐Arg‐Arg sequence at position 707 of the IGF‐I receptor precursor will generate alpha (80,423 Mr) and beta (70,866 Mr) subunits, which compare with approximately 135,000 Mr (alpha) and 90,000 Mr (beta) fully glycosylated subunits.

Many lower vertebrates exhibit colour change in response to the background. A dual hormonal control of colour change by two antagonistic pituitary melanophorotropic hormones was first postulated in amphibia by Hogben and Slome. It is well established that the melanotropins alpha- and beta-MSH are responsible for pigment dispersion in the integumentary melanophore of lower vertebrates and that these molecules are derived from a common precursor protein, proopiocortin, by specific processing within the intermediate lobe. No evidence has been found for an antagonistic hormone in amphibia, although the existence of such a molecule in the pituitary gland of teleost fishes has long been recognized and was termed the melanophore-concentrating hormone by Enami. Early attempts to separate the two hormones proved unsuccessful. Recently, Baker and Ball re-invoked the dual hormone concept, and it has been suggested that a melanin-concentrating hormone (MCH) is synthesized in the hypothalamus of teleosts and stored and released by the neurohyphophysis. We have now isolated a novel peptide from the pituitary of the salmon (Oncorhynchus keta) possessing an antagonistic function to MSH, and we describe here its chemical and biological characteristics.

This study examined the effect of aging on adrenal cell function in Sprague-Dawley rats, as judged by the binding of iodinated Phe2, Nle4-ACTH-(1-38) to the adrenal cells, and the ability of the cells to respond to ACTH stimulation by the production of cAMP and corticosterone in vitro. Collagenase-dispersed adrenal cells obtained from 2-, 12-, and 18-month-old-rats were used. The maximum corticosterone concentration after incubation with ACTH was significantly lower (P less than 0.001) in the 12-month-old (40 +/- 7 ng/micrograms DNA) and 18-month-old rats (28 +/- 3 ng/micrograms DNA) compared to that in 2-month-old controls (102 +/- 9 ng/micrograms DNA). The ED50 values of ACTH-induced corticosterone production measured in the cell suspension were similar in 2- and 12-month-old groups (30 pg/ml), and the diminished production of corticosterone in the 12-and 18-month-old rats persisted after incubation with N6,O2-dibutyryl cAMP. Neither the number nor the binding affinity of adrenal receptors for [125I]I-Tyr23,Phe2,Nle4-ACTH-(1-38) changed from 2-12 months of age. Furthermore, increases in concentrations of intra- and extracellular cAMP after ACTH stimulation were not significantly different in the 2-, 12-, and 18-month-old groups. Similarly, adrenal hydrolysis of cAMP by low and high Km phosphodiesterases did not change significantly with advancing age. These results provide strong evidence that there is a diminished capacity for corticosterone production with aging in the rat, and that the site of the defect lies distal to binding of trophic hormone to its receptor and to the production of its secondary messenger. Finally, an age-related decline in adrenal steroidogenic capacity could be viewed as a counterregulatory mechanism invoked in old rats to compensate, at least partially, for elevated plasma ACTH and corticosterone concentrations.