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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS028019-02
Application #
3414492
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1990-07-06
Project End
1995-06-30
Budget Start
1991-07-01
Budget End
1992-06-30
Support Year
2
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Missouri Kansas City
Department
Type
Schools of Medicine
DUNS #
800772162
City
Kansas City
State
MO
Country
United States
Zip Code
64110
Chronwall, B M; Sands, S A; Cummings 3rd, K C et al. (2000) Glial somatostatin-14 expression in the rat pituitary intermediate lobe: a possible neurotrophic function during development? Int J Dev Neurosci 18:685-92
Beatty, D M; Morris, S J; Chronwall, B M (1998) Heterogeneity in POMC expression among explanted melanotropes decreases with time in culture and bromocriptine treatment. Peptides 19:659-65
Sands, S A; de Blas, A L; Chronwall, B M (1998) Dopamine D2 receptor effects on GABA(A) receptor expression may modify melanotrope peptide release. Peptides 19:397-401
Chronwall, B M; Sands, S A; Cummings 3rd, K C et al. (1998) Differential innervation of individual melanotropes suggests a role for nonsynaptic inhibitory regulation of the developing and adult rat pituitary intermediate lobe. Synapse 28:227-43
Sharma, P; Hagler, K E; Dybdal, N O et al. (1997) Salt-loading induces decreased POMC mRNA levels, increased alpha-MSH immunoreactivity, and sustained elevated fos expression in rat pituitary intermediate lobe melanotropes. Ann N Y Acad Sci 814:295-9
Sands, S A; Le Mon, D; Chronwall, B M (1997) Lactation and salt loading similarly alter neuropeptide Y, but differentially alter somatostatin, in separate sets of rat neural lobe axons. Peptides 18:1045-50
Beatty, D M; Sands, S A; Morris, S J et al. (1996) Types and activities of voltage-operated calcium channels change during development of rat pituitary neurointermediate lobe. Int J Dev Neurosci 14:597-612
Chronwall, B M; Sands, S A; Dickerson, D S et al. (1996) Melanotrope dopamine D2 receptor isoform expression in the developing rat pituitary. Int J Dev Neurosci 14:77-86
Sands, S A; Gary, K A; Chronwall, B M (1995) Transient expression of S-100 by melanotropes of the rat pituitary intermediate lobe during development. Int J Dev Neurosci 13:567-76
Gary, K A; Sands, S A; Chronwall, B M (1995) Glial-like cells of the rat pituitary intermediate lobe change morphology and shift from vimentin to GFAP expression during development. Int J Dev Neurosci 13:555-65

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