Hmgcr in the Corpus Allatum Controls Sexual Dimorphism of Locomotor Activity and Body Size via the Insulin Pathway in Drosophila

The insulin signaling pathway has been implicated in several physiological and developmental processes. In mammals, it controls expression of 3-Hydroxy-3-Methylglutaryl CoA Reductase (HMGCR), a key enzyme in cholesterol biosynthesis. In insects, which can not synthesize cholesterol de novo, the HMGCR is implicated in the biosynthesis of juvenile hormone (JH). However, the link between the insulin pathway and JH has not been established. In Drosophila, mutations in the insulin receptor (InR) decrease the rate of JH synthesis. It is also known that both the insulin pathway and JH play a role in the control of sexual dimorphism in locomotor activity. In studies here, to demonstrate that the insulin pathway and HMGCR are functionally linked in Drosophila, we first show that hmgcr mutation also disrupts the sexual dimorphism. Similarly to the InR, HMGCR is expressed in the corpus allatum (ca), which is the gland where JH biosynthesis occurs. Two p[hmgcr-GAL4] lines were therefore generated where RNAi was targeted specifically against the HMGCR or the InR in the ca. We found that RNAi-HMGCR blocked HMGCR expression, while the RNAi-InR blocked both InR and HMGCR expression. Each RNAi caused disruption of sexual dimorphism and produced dwarf flies at specific rearing temperatures. These results provide evidence: (i) that HMGCR expression is controlled by the InR and (ii) that InR and HMGCR specifically in the ca, are involved in the control of body size and sexual dimorphism of locomotor activity

Diabetogenic action of pituitary hormones on adrenalectomized hypophysectomized dogs

THE diabetogenic action of the anterior pituitary extracts was demonstrated in hypophysectomized-pancreatectomized toads by Houssay and Biasotti (1). This action was not obtained in pancreatectomized cats and rats in the absence of adrenals (2, 3). But the diabetogenic action of the anterior pituitary extract was obtained in other adrenalectomized animals : a) toads deprived of adrenals and pancreas (4); b) toads deprived of hypophysis, pancreas, kidney and adrenals (5): c) toads deprived of hypophysis, pancreas and adrenals (4, 6); in cases 6 and c, the diabetogenic action was diminished by the absence of the adrenals. The diabetogenic action of the pituitary was also observed in mammals deprived of the adrenals such as: d) dogs with reduction of the pancreatic mass, deprived of both adrenals and maintained with cortico-adrenal extract (7, 8) or with desoxycorticosterone (8); e) dogs with reduction of the pancreatic mass, deprived of the adrenals, maintained only with sodium chloride and not receiving adrenal hormones (8); some of these dogs were also deprived of the thyroid. All these experiments demonstrated that hypophyseal diabetes may be obtained without the presence or participation of the adrenals.Fil: Houssay, Bernardo Alberto. Fundación de Instituto de Biología y Medicina Experimental; ArgentinaFil: Penhos, J. C.. Fundación de Instituto de Biología y Medicina Experimental; Argentinafond

Action of the hypoglycemic sulfonyl compounds in hypophysectomized, adrenalectomized, and depancreatized animals

The effect produced by extirpation of the pituitary, adrenal, and pancreas on the effect of four hypoglycemic sulfonyl compounds was estudied in dogs, rats, and toads. A fall of blood sugar was observed in normal, hypophyesctomized, adrenalectomized, and castrated male or female dogs. Except in a few cases, the effect could not be obtained in depancreatized dogs unless a small fragment of the organ remained.Fil: Houssay, Bernardo Alberto. Fundación de Instituto de Biología y Medicina Experimental; ArgentinaFil: Penhos, J. C.. Fundación de Instituto de Biología y Medicina Experimental; ArgentinaFil: Teodosio, N.. Fundación de Instituto de Biología y Medicina Experimental; ArgentinaFil: Bowkett, J.. Fundación de Instituto de Biología y Medicina Experimental; ArgentinaFil: Apelbaum, J.. Fundación de Instituto de Biología y Medicina Experimental; Argentinafond

The role of insulin in the action of the hypoglycemic sulfonyl compounds

In the preceding paper it was reported that hypoglycemic sulfonyl compounds did not produce a significant decrease in the blood sugar level in the absence of the pancreas (16 depancreatized dogs and 9 hypophysectomizeddepancreatized dogs).Fil: Houssay, Bernardo Alberto. Fundación de Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología; ArgentinaFil: Penhos, J. C.. Fundación de Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología; ArgentinaFil: Urgoiti, E.. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología; Argentina. Fundación de Instituto de Biología y Medicina Experimental; ArgentinaFil: Teodosio, N.. Fundación de Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología; ArgentinaFil: Apelbaum, J.. Fundación de Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología; ArgentinaFil: Bowkett, J.. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología; Argentina. Fundación de Instituto de Biología y Medicina Experimental; Argentinafond