Steroid hormone secretion in insects comes of age

The control of molting and metamorphosis in insects first captured the attention of physiologists in the 1920s, when the Polish physiologist Stephan Kopec showed that the brain stimulated molting in larvae of the gypsy moth (1). However, 70 years elapsed before the hormone from the brain, prothoracicotropic hormone (PTTH), was finally sequenced by groups led by H. Ishizaki and A. Suzuki (2). During the interim, it was shown that the brain’s role in causing molting was not direct but was mediated through its action on paired endocrine glands in the thorax, the prothoracic glands (PGs), that then secreted a steroid molting hormone, ecdysone. Circulating PTTH acts on these glands to stimulate steroidogenesis via calcium entry and cAMP generation (3) in a manner similar to that seen in some vertebrate steroidogenic systems. Although the control of ecdysone secretion by a circulating tropic hormone has been a central concept in comparative endocrinology for >40 years, a series of recent articles have revealed that negative factors are also at play (4–6). The article by Yamanaka et al . (7) in a recent issue of PNAS described some novel peptides that exert inhibitory control on the PGs and showed that the pathway by which they exert their effects is through the direct innervation of the glands. The simple picture of PG control in insects arose from the simplicity of the system first used to elucidate the brain–PG axis. Pioneering work by Carroll Williams (8) exploited diapausing pupae of the giant silkmoth, Hyalophora cecropia , whose development shuts down early in metamorphosis to deal with the rigors of winter. To then activate adult differentiation in the spring, the dormant PGs required PTTH released from the brain, and diapausing pupae whose brains were surgically removed never resumed development, although they survived for months (8 … *E-mail: jwt{at}u.washington.edu