Dopaminergic regulation of the biosynthetic activity of individual melanotropes in the rat pituitary intermediate lobe: a morphometric analysis by light and electron microscopy and in situ hybridization.

The primary cell type of the intermediate lobe (IL) of the rat pituitary is a polyhedral secretory cell with a smooth ovoid nucleus. The results of this study demonstrate, however, that IL melanotropes are a heterogeneous cell population. Melanotropes differed in the tinctorial properties of their cytoplasm; some cells appeared distinctly darker, others lighter, and cells staining in intermediate shades were also found. Electron microscopical morphometry revealed that darkly staining melanotropes have a denser cytosol and contain a greater amount of rough endoplasmic reticulum, mitochondria, and secretory vesicles than light cells. In addition, in situ hybridization studies, using a POMC probe, showed that POMC mRNA was distributed unevenly among melanotropes in a pattern comparable to the distribution of light and dark cells. These studies further demonstrated that dopaminergic drug treatments, which are known to alter the secretion of POMC-related peptides from the IL, produced parallel changes in both the histological staining properties and the amount of POMC mRNA per cell. Haloperidol treatment dramatically increased the number of dark melanotropes and the amount of POMC mRNA in each cell and eliminated the cellular heterogeneity in both staining properties and the distribution of POMC mRNA. After bromocriptine treatment the number of light melanotropes increased, and each cell contained reduced levels of POMC mRNA. These findings indicate that individual melanotropes maintain different levels of biosynthetic activity and that treatments that alter the secretion of POMC peptides affect both the rate of POMC synthesis in individual melanotropes and the cellular heterogeneity of the IL.