Abstract

This research seeks to further elucidate the role of tuberoinfundibular dopaminergic (TIDA) neurons in the release of prolactin (PRL) from the anterior pituitary gland in the rat. A microdissection technique has been introduced which allows for the discrete removal of nuclei, terminal projection fields and fiber pathways from the rat brain. The development of highly sensitive radioisotopic-enzymatic assays for dopamine (DA), norepinephrine (NE) and 3,4-dihydroxyphenylacetic acid (DOPAC) now allow for the determination of DA and NE turnover and the major DA metabolite DOPAC in such microdissected brain regions. In concert, these microtechniques allow for the neurochemical analysis of neuroendocrine events at a level of resolution far greater than previously possible. Neuronal activity will be assessed by two neurochemical indices: (1) the determination of DA and NE turnover (alpha-methyl-para-tyrosine method), and (2) measurement of DOPAC tissue concentrations. The neurochemical dynamics of TIDA terminals in the median eminence (ME) will be contrasted with other known dopaminergic projections to the caudate nucleus, olfactory tubercle and medial preoptic nucleus during controlled endocrine manipulations of PRL secretion. Changes specific to TIDA neurons may thus be identified and correlated with PRL titers in the peripheral circulation as determined by direct radioimmunoassay. A neurochemical analysis of the suckling-induced rise in PRL will be undertaken entailing estimation of TIDA neuronal activity during this dramatic neuroendocrine response. The short-loop negative feedback action of PRL on TIDA neurons will be investigated in hypophysectomized rats. A neural site of action of 2-brom-alpha-ergocryptine (CB-154), a drug used clinically to inhibit PRL secretion and in the treatment of Parkinson's disease, will be investigated at the level of the TIDA neurons. These experiments bear on the working hypothesis that TIDA neurons function as prolacting inhibitory factor (PIF) neurosecretory neurons.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD021351-09
Application #
3320231
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1978-07-01
Project End
1990-06-30
Budget Start
1987-07-01
Budget End
1990-06-30
Support Year
9
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of Maryland Baltimore
Department
Type
Schools of Medicine
DUNS #
003255213
City
Baltimore
State
MD
Country
United States
Zip Code
21201

  Publications

Joh, Hung-Dong; Searles, Robin V; Selmanoff, Michael et al. (2006) Estradiol alters only GAD67 mRNA levels in ischemic rat brain with no consequent effects on GABA. J Cereb Blood Flow Metab 26:518-26
Yoo, M J; Searles, R V; He, J R et al. (2000) Castration rapidly decreases hypothalamic gamma-aminobutyric acidergic neuronal activity in both male and female rats. Brain Res 878:10-Jan
Searles, R V; Yoo, M J; He, J R et al. (2000) Sex differences in GABA turnover and glutamic acid decarboxylase (GAD(65) and GAD(67)) mRNA in the rat hypothalamus. Brain Res 878:9-Nov
Grattan, D R; Selmanoff, M (1997) Sex differences in the activity of gamma-aminobutyric acidergic neurons in the rat hypothalamus. Brain Res 775:244-9
Grattan, D R; Rocca, M S; Sagrillo, C A et al. (1996) Antiandrogen microimplants into the rostral medial preoptic area decrease gamma-aminobutyric acidergic neuronal activity and increase luteinizing hormone secretion in the intact male rat. Endocrinology 137:4167-73
Park, S K; Strouse, D A; Selmanoff, M (1996) Prolactin- and testosterone-induced inhibition of LH secretion after orchidectomy: role of catecholaminergic neurones terminating in the diagonal band of Broca, medial preoptic nucleus and median eminence. J Endocrinol 148:291-301
Grattan, D R; Rocca, M S; Strauss, K I et al. (1996) GABAergic neuronal activity and mRNA levels for both forms of glutamic acid decarboxylase (GAD65 and GAD67) are reduced in the diagonal band of Broca during the afternoon of proestrus. Brain Res 733:46-55
Grattan, D R; Park, S K; Selmanoff, M (1995) Orchidectomy and NMDA increase GnRH secretion as measured by push-pull perfusion of rat anterior pituitary. Am J Physiol 268:E685-92
Grattan, D R; Selmanoff, M (1994) Prolactin- and testosterone-induced inhibition of LH secretion after orchidectomy: role of preoptic and tuberoinfundibular gamma-aminobutyric acidergic neurones. J Endocrinol 143:165-74
Park, S K; Grattan, D R; Selmanoff, M (1993) Differential effects of adrenalectomy on the prolactin-induced suppression of LH and FSH secretion after castration in male rats. J Reprod Fertil 99:209-17

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