skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Bromocryptine prevents the decline in tuberoinfundibular neuronal release of dopamine after removal of chronic estrogen treatment

Abstract

Prolonged exposure to estradiol 17-..beta.. (E/sub 2/) in rats has been shown to decrease dopamine (DA) synthesis in and release from tuberoinfundibular dopaminergic (TIDA) neurons in Fischer 344 rats. The objective of the present study was to determine whether inhibition of the E/sub 2/-induced increase in anterior pituitary (AP) weight and prolactin (PRL) secretion by concomitant administration of the dopaminergic agonist, bromocryptine, could prevent the decrease in TIDA neuronal function produced by chronic E/sub 2/ administration. TIDA neuronal function was evaluated by in vitro superfusion and electrical stimulation of median eminence (ME) tissue after allowing for accumulation of (/sup 3/H) dopamine (DA). The effect of chronic E/sub 2/ and/or bromocryptine treatment on catecholamine content in tuberohypophyseal neurons in the neurointermediate lobe was also measured to determine whether increased pituitary size possibly damaged the tuberohypophyseal neurons.

Authors:
;
Publication Date:
Research Org.:
Michigan State Univ., East Lansing (USA)
OSTI Identifier:
5272055
Resource Type:
Journal Article
Resource Relation:
Journal Name: Proc. Soc. Exp. Biol. Med.; (United States); Journal Volume: 186:2
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; DOPAMINE; BIOSYNTHESIS; ENZYME INHIBITORS; BIOLOGICAL EFFECTS; ESTRADIOL; BIOLOGICAL FUNCTIONS; CATECHOLAMINES; CHRONIC EXPOSURE; INHIBITION; LTH; NERVE CELLS; PITUITARY GLAND; TRACER TECHNIQUES; TRITIUM COMPOUNDS; AMINES; ANIMAL CELLS; AROMATICS; AUTONOMIC NERVOUS SYSTEM AGENTS; BODY; CARDIOTONICS; CARDIOVASCULAR AGENTS; DRUGS; ENDOCRINE GLANDS; ESTRANES; ESTROGENS; FUNCTIONS; GLANDS; GONADOTROPINS; HORMONES; HYDROXY COMPOUNDS; ISOTOPE APPLICATIONS; LABELLED COMPOUNDS; NEUROREGULATORS; ORGANIC COMPOUNDS; ORGANS; PEPTIDE HORMONES; PHENOLS; PITUITARY HORMONES; POLYPHENOLS; SOMATIC CELLS; STEROID HORMONES; STEROIDS; SYMPATHOMIMETICS; SYNTHESIS; 550201* - Biochemistry- Tracer Techniques

Citation Formats

Gottschall, P.E., and Meites, J. Bromocryptine prevents the decline in tuberoinfundibular neuronal release of dopamine after removal of chronic estrogen treatment. United States: N. p., 1987. Web. doi:10.3181/00379727-186-42595.
Gottschall, P.E., & Meites, J. Bromocryptine prevents the decline in tuberoinfundibular neuronal release of dopamine after removal of chronic estrogen treatment. United States. doi:10.3181/00379727-186-42595.
Gottschall, P.E., and Meites, J. 1987. "Bromocryptine prevents the decline in tuberoinfundibular neuronal release of dopamine after removal of chronic estrogen treatment". United States. doi:10.3181/00379727-186-42595.
@article{osti_5272055,
title = {Bromocryptine prevents the decline in tuberoinfundibular neuronal release of dopamine after removal of chronic estrogen treatment},
author = {Gottschall, P.E. and Meites, J.},
abstractNote = {Prolonged exposure to estradiol 17-..beta.. (E/sub 2/) in rats has been shown to decrease dopamine (DA) synthesis in and release from tuberoinfundibular dopaminergic (TIDA) neurons in Fischer 344 rats. The objective of the present study was to determine whether inhibition of the E/sub 2/-induced increase in anterior pituitary (AP) weight and prolactin (PRL) secretion by concomitant administration of the dopaminergic agonist, bromocryptine, could prevent the decrease in TIDA neuronal function produced by chronic E/sub 2/ administration. TIDA neuronal function was evaluated by in vitro superfusion and electrical stimulation of median eminence (ME) tissue after allowing for accumulation of (/sup 3/H) dopamine (DA). The effect of chronic E/sub 2/ and/or bromocryptine treatment on catecholamine content in tuberohypophyseal neurons in the neurointermediate lobe was also measured to determine whether increased pituitary size possibly damaged the tuberohypophyseal neurons.},
doi = {10.3181/00379727-186-42595},
journal = {Proc. Soc. Exp. Biol. Med.; (United States)},
number = ,
volume = 186:2,
place = {United States},
year = 1987,
month =
}
  • The objective of these studies was to determine if the decline in tuberoinfundibular dopaminergic (TIDA) neuronal function observed during chronic estradiol-17-..beta.. (E/sub 2/) administration persisted after E/sub 2/ was removed. Ovariectomized (OVX) Fischer 344 rats were implanted with an E/sub 2/-containing Silastic capsule for 4 weeks. Anterior pituitary (AP) weight and serum prolactin was greatly increased at the end of the E/sub 2/ treatment, that persisted 4 and 26 weeks after E/sub 2/ was withdrawn. Ag the end of E/sub 2/ treatment and 4 weeks after E/sub 2/ was withdrawn, TIDA function, as evaluated by electrical stimulation of median eminencemore » tissue in vitro after allowing for uptake of /sup 3/H-DA, was decreased compared to OVX controls. In an attempt to elucidate the mechanism by which E/sub 2/ results in a permanent decline in TIDA function, F344 rats were given daily bromocryptine injections in addition to a 30-day E/sub 2/ treatment. TIDA neuronal release was reduced in both E/sub 2/ and E/sub 2/ and bromocryptine treated groups. However, by 30 days after discontinuing treatment only rats given E/sub 2/ alone showed a persistent decline in TIDA function. Since permanent damage to hypothalamic neurons by an enlarged AP was speculated to be the result of E/sub 2/ treatment, neurons which regulate other AP hormones may also be damaged. To evaluate this possibility, pulsatile release of prolactin, growth hormone (GH) and luteinizing hormone (LH) was evaluated in OVX control rats, chronically E/sub 2/-treated rats, and rats 120 days after chronic E/sub 2/ treatment. Only the frequency of prolactin pulses, but not the frequency of GH and LH pulses, was reduced in rats 120 days after E/sub 2/ treatment. This suggests selectivity in the hypothalamic damage produced by the enlarged AP.« less
  • In the present study we investigated the effect of amiloride, a rather specific inhibitor of the membrane Na+-Ca++ exchange system, on the release of endogenous dopamine (DA) and previously taken-up (3H)DA from tuberoinfundibular dopaminergic neurons. Amiloride (300 microM) stimulated either endogenous DA or (3H)DA release. Amiloride-induced stimulation of (3H)DA release was prevented in a Ca++-free plus ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid medium. Amiloride, at the same concentration, reinforced both high K+- and electrically-induced stimulation of (3H)DA release. These results are explained on the basis of the ability of amiloride in blocking the Na+-Ca++ exchange system, therefore causing an elevation ofmore » intracellular Ca++ levels in resting conditions, and a further accumulation of Ca++ ions after high K+- or electrically elicited opening of voltage-operated channels specific for Ca++ ions. The enhanced intracellular Ca++ availability may trigger the stimulation of neurotransmitter release. In addition, amiloride was able to block in a dose-dependent manner (70-300 microM) the ouabain-induced (3H)DA release, suggesting that, when intracellular concentrations of Na+ are increased by the blockade of Na+,K+-adenosine triphosphatase the Na+-Ca+;+ exchange carrier reverses its resting mode of operation, mediating the influx of extracellular Ca++ ions. Amiloride, by blocking the Na+-Ca++ exchange mechanism, prevents the ouabain-elicited entrance of extracellular Ca++ ions, therefore inhibiting (3H)DA release stimulated by the cardioactive glycoside. Collectively, the results of the present study seem to be compatible with the idea that the Na+-Ca++ exchange mechanism is involved in the regulation of (3H)DA release from tuberoinfundibular dopaminergic neurons, through the regulation of Ca++ movements across the plasma membrane.« less
  • In the present study we investigated the membrane events and the ionic processes which mediate the stimulatory effect of ouabain on the release of endogenous dopamine (DA) and previously taken-up (3H)DA release from rat hypothalamic tuberoinfundibular dopaminergic (TIDA) neurons. Ouabain (0.1-1 mM) dose-dependently stimulated endogenous DA and newly taken-up (3H)DA release. This effect was counteracted partially by nomifensine (10 microM). Removal of Ca++ ions from the extracellular space in the presence of the Ca++-chelator ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid prevented completely ouabain-elicited (3H)DA release. Lanthanum (1 mM) and cobalt (2 mM), two inorganic Ca++-entry blockers, were able to inhibit thismore » stimulatory effect, whereas verapamil (10 microM) and nitrendipine (50 microM), two organic antagonists of the voltage-operated channel for Ca++ ions, failed to affect ouabain-induced (3H)DA release. By contrast, adriamycin (100-300 microM), a putative inhibitor of cardiac Na+-Ca++ antiporter, dose-dependently prevented ouabain-induced (3H)DA release from TIDA neurons. Finally, tetrodotoxin reduced digitalis-stimulated (3H)DA release. In conclusion, these results seem to be compatible with the idea that the inhibition of Na+,K+-adenosine triphosphatase by ouabain stimulates the release of (3H)DA from a central neuronal system like the TIDA tract and that this effect is critically dependent on the entrance of Ca++ ions into the nerve terminals of these neurons. In addition the Na+-Ca++ exchange antiporter appears to be the membrane system which transports Ca++ ions into the neuronal cytoplasm during Na+,K+-adenosine triphosphatase inhibition. The enhanced intracellular Ca++ availability triggers DA release which could occur partially through a carrier-dependent process.« less
  • The dopamine transport system in the tuberoinfundibular tract of the spontaneously hypertensive (SHR), Wistar Kyoto (WKY) and Sprague-Dawley (SD) rats was investigated. The results show that the rate of dopamine transport in this tract is strain-specific. SD rats transported twice as much dopamine (in 30 minutes) as WKY and SHR. The dopamine transport system in the SHR, being at par with that of the WKY, remained intact. These findings suggest that hypertension and the alleged reduced central dopaminergic activity in the SHR is not related to the transport of dopamine in the tuberoinfundibular tract.
  • The role that estrogen plays in the regulation of corticotropin-releasing factor (CRF) is not known. A radioimmunoassay specific for rat CRF was utilized to measure the CRF-like immunoreactivity (CRF-ir) in the hypothalamus of ovariectomized rats treated with estradiol for periods up to 12 weeks. Compared to ovariectomized controls, estradiol treatment resulted in significantly reduced CRF-ir after 3 and 12 weeks, although no significant change was seen after 8 weeks. Anterior pituitary (AP) weight was greatly increased by estradiol treatment at all time points studied. Bromocriptine treatment for the last 3 weeks of the 12-week period, or removal of estradiol formore » 3 weeks after 9 weeks of treatment did not reverse the changes in CRF-ir even though significant regressions of tumor size was achieved. There was no correlation between AP weight and CRF-ir in individual animals. These data show that chronic treatment with estrogen reduced hypothalamic CRF-ir content. Neither a direct estrogenic effect or an indirect effect mediated through alterations in the adenohypophysis could be ruled out. 21 references, 3 figures.« less