Mechanisms of action of the synthetic hypertrehalosemic hormone in the fat body of the cockroach, Blaberus discoidalis

Abstract

The hypertrehalosemic hormone (HTH) is a decapeptide that is stored and released from corpora cardiaca (CC) of the cockroach, Blaberus discoidalis. HTH has at least three distinct physiological actions on the fat body. One is to mobilize storage glycogen by activating glycogen phosphorylase. This results in the synthesis of trehalose, the main circulatory carbohydrate. The second is to stimulate heme synthesis during mitochondriogenesis. The third effect is to stimulate gene expression for a new cytochrome P450 (CYP4C1). Intracellular transduction studies reveal that cAMP is not the second messenger of HTH for hypertrehalosemia, nor are cGMP, diacylglycerol or calcium. Extracellular calcium is required for HTH activation of glycogen phosphorylase but is not active by itself. cGMP is the intracellular mediator for HTH in the activation of the CYP4C1 gene based on (i) the direct stimulatory effect of HTH on guanylate cyclase activity and on cytosol cGMP levels, and (ii) a mimicking effect by a cGMP analog on the increase of CYP4C1 message. Expression of the CYP4C1 gene is also regulated by several factors in addition to HTH. For example, starvation and castration have strong stimulatory effects on CYP4C1 gene expression suggesting that CYP4C1 activity is associated with physiological status. Starvation-stimulated CYP4C1 gene expression may result from a stress-induced release of HTH from the CC. 20-hydroxyecdysone also increases levels of the CYP4C1 message; Manduca adipokinetic hormone and juvenile hormone III do not. The functional significance of CYP4C1 may be the generation of gluconeogenic substrates from fatty acids during stress and perhaps the conversion of glycogenolytic products to trehalose.