The turbero-hypophyseal axis is characterized by limited neuronal complexity and few trans-interactions with a homogenous target tissue which produces only one major prohormone (POMC). We have demonstrated that the biosynthetic activity of intermediate lobe (IL) melanotropes is regulated by dopaminergic inhibition. Dopamine mitochondria; POMC mRNA levels and mitotic rate. DA antagonists have the opposite effect. The objective of this project is to establish how axons containing the colocalized neurotransmitters DA and gamma- aminobutyric acid (GABA) regulate the melanotropes. This system provides an excellent vehicle to study the mechanisms of transsynaptic regulation by colocalized neurotransmitters of peptide biosynthesis, biosynthetic heterogeneity and cellular hyperplasia.
The specific aims are: (1) To morphologically characterize IL neuronal terminals and to quantitatively described their distribution and GABA/DA content, using light- and electron microscopic immunohistochemistry and morphometry. (2) To quantitate both in vitro and in vivo the effects of GABA on melanotrope biosynthetic potential hormone secretion and mitotic rate. The methods to be employed are in situ hybridization histochemistry, using a pro-opiomelanocortin (POMC) probe, RIA and incorporation of [3H] thymidine resolved at the single cell level. (3) To evaluate modulatory interactions between GABA and DA on POMC mRNA, hormone secretion (by RIA) and mitotic rate in the IL. (4) To determine the time sequence of the appearance of GABA and DA and to evaluate differing roles of the neurotransmitters during ontogeny, (immunohistochemistry, morphometry, [3H] thymidine incorporation, in situ hybridization histochemistry using a POMC probe). Studies of the effects of colocalized transmitters are of great importance for the understanding of the wide diversity of modulatory possibilities inherent in neuronal regulation. Comprehension of the mechanism of cotransmitter action is a necessary step in understanding normal neuronal regulation; human neurological and psychological diseases; and subsequently, how to treat such disorder without adverse drug effects emanating from interference with colocalized neurotransmitters.
Showing the most recent 10 out of 20 publications
