Karen A. Gregerson, Ph.D.
Laboratory of Cellular Neuroendocrinology
The female reproductive cycle is the result of the dynamic interplay of hormones in the brain-pituitary-ovarian axis. The secretion of any one hormone is subject to continual modification by a variety of other hormones and neurotransmitters. These modulators often demonstrate multiple actions on target cells and/or actions on multiple cell types. The goal of our work in this laboratory is to understand the regulation of hormone secretion from endocrine cells, particularly prolactin. To this end, we are examining the membrane and intracellular events involved in the process of excitation-secretion coupling in prolactin-secreting cells. Our research utilizes (1) immunological assays to identify and quantitate secretory activity of single cells, (2) fluorescence microscopy using specialized probes to directly measure and image cytosolic calcium within individual cells, (3) electrophysiological techniques to examine membrane excitability and ionic conductances, and (4) molecular biological techniques to identify candidate gene products involved in these processes. Such a multifaceted investigation greatly improves our understanding of the regulation of a secretory event. For example, work from our laboratory has shown that dopamine, the major physiological regulator of prolactin secretion, activates a K+ channel (KDA) in the membrane of prolactin-secreting cells. The activation of KDA and the associated electrical changes are critical mechanisms in regulating cytosolic [Ca2+] and prolactin secretion. Finally, this dopamine-activated K+ current is present only during certain endocrine states and can be induced by estrogen. This may explain a long-recognized but poorly understood modulation of dopamine’s efficacy by estrogen. These findings have opened a new avenue of investigation for our laboratory: using molecular cloning techniques and structure function studies, we have recently identified two gene products which appear to oligomerize to form the KDA channel. Using this molecular information, we are developing transgenic mouse lines in which the function of KDA will be selectively disrupted in pituitary lactotropes. Such animal models will provide the ultimate "system" for evaluation of the physiological role of KDA in the regulation of prolactin secretion.
Recent Publications:
Gregerson KA, Golesorkhi N, Chuknyiska R 1994a Mechanism of augmented prolactin release by dopamine withdrawal: I. Role of membrane hyperpolarization. American Journal of Physiology 267:E781-E788.
Gregerson KA 1995 Complement action on secretory cells identified by the reverse hemolytic plaque assay: Modified assay eliminates exposure of cells to complement. Endocrine 3:371-376.
Ho MY, Kao JPY, Gregerson KA 1996 Dopamine withdrawal elicits prolonged calcium rise to support prolactin rebound release. Endocrinology 137:3513-3521.
Gregerson KA, Flagg TP, Anderson M, Lauring O, Welling PA Identification of G-protein-coupled, inward rectifier potassium channel gene products from the rat anterior pituitary gland. Endocrinology, in press.
