Priscilla Dannies, PhD

A major unanswered question in endocrinology is how protein hormones are concentrated into secretory granules. We have developed a model system of rat pituitary tumor cells, GH4C1 cells, which have few secretory granules, but can be induced to accumulate many and to store prolactin. We have identified mutants of human prolactin and human growth hormones that can not be stored themselves, and that interfere with the storage or stability of wild-type hormones.

We are investigating why these mutants behave as they do by physical techniques in solution and biochemical methods in cells. Dominant-negative mutants for secretion of hormones have been found in people deficient in growth hormone, vasopressin and amylin. Understanding how mutants of prolactin and growth hormone interfere with synthesis and storage or normal hormones will lead to understanding the mechanisms of these eficiencies as well as answering a basic question in endocrinology.