The melanophore-stimulating hormone (MSH) cells of the amphibian pars intermedia secrete the peptide a-melanophore-stimulating hormone (a-MSH), which induces pigment dispersion in dermal melanophores. The purpose of the present study was to determine (1) whether prolonged activation of the secretory activity of the pars intermedia is associated with hypertrophy, hyperplasia, or both and (2) whether the MSH cells function as a homo geneous or heterogeneous population in meeting the physiological demand for MSH. The demand for MSH was manipulated by adapting animals for at least 3 weeks to white, two shades of grey, or black backgrounds. Morphometric analysis showed that the intermediate lobe volume was positively correlated with the degree of pigment dispersion in the mela nophores. The number of MSH cells per lobe was not affected by the degree of pigment dispersion. Therefore, we conclude that enlargement of the tissue associated with MSH cell activation involves hypertrophy rather than hyperplasia. Ultrastructural examination indi cated that the majority of MSH cells in black-adapted animals are biosynthetically active, whereas the cells of white-adapted animals are relatively inactive and show granule storage. The pars intermedia of grey-adapted toads contained both active and inactive cells, indi cating that MSH cells respond as a heterogeneous cell population in meeting the endocrine demand imposed by background. © 1990 Academic Press, inc.In general, activation of endocrine cells may involve hypertrophy, hyperplasia, or both. Furthermore, two patterns of cell re sponses can be distinguished during activa tion: either all cells become activated or only subpopulations of cells become acti vated. An example of the former are the oxytocin-producing neuroendocrine cells that respond as a homogeneous population to the suckling stimulus (Poulain and Wakerley, 1982). An example of the latter are the vasopressin-producing neuroendocrine cells that respond as a heterogeneous pop ulation to osmotic stress (Poulain and Wakerley, 1982). Morphometric and biochemi cal evidence has been advanced that the rat gonadotropes and lactotropes (Lucque et al., 1986) as well as the p cells of the pancreatic islets (Schuit et al., 1988) and thyroid follicular cells in mice (Gerber et al., 1987) form heterogeneous populations with regard to their secretory response to demand for hormone.In the present investigation we studied the response of amphibian melanophorestimulating hormone (MSH)-producing cells to a physiological stimulus. Two major questions were addressed. First, does the activation of the pars intermedia involve hypertrophy, hyperplasia, or both? Second, do the endocrine cells of this tissue function as a homogeneous or as a heterogeneous cell population in response to a demand for MSH? The MSH cell of Xenopus laevis provides a good model to study these ques tions because the pars intermedia activity can be easily manipulated. The MSH cells of animals placed on a black background release a-MSH, which stimulates pigment ...