Functional interrelationships between adrenergic and opioid systems in the neuroregulation of growth hormone
V M Arce1, S G Cella, V Locatelli
1Department of Pharmacology, Chemotherapy and Toxicology, University of Milan, 20129 Milan, Italy.
Insights
Opioid peptides and adrenergic systems influence growth hormone (GH) release in rat pups through separate pathways. Opioid stimulation enhances GH release without tolerance, while adrenergic stimulation impacts basal GH levels.
Area of Science:
- Neuroendocrinology
- Developmental Biology
- Pharmacology
Background:
- The hypothalamic control of growth hormone (GH) secretion involves complex interactions between various neurochemical systems.
- Understanding the interplay between adrenergic and opioid systems is crucial for elucidating developmental regulation of GH release.
Purpose of the Study:
- To investigate the functional interrelationships between hypothalamic adrenergic and opioid systems in regulating GH release in 10-day-old rats.
- To determine the distinct roles of alpha(2)-adrenoceptors and opioid receptors in mediating GH secretion and synthesis.
Main Methods:
- Administration of clonidine (alpha(2)-adrenoceptor agonist) and FK 33-824 (opioid receptor agonist) to assess their effects on plasma GH levels.
- Pharmacological blockade using naloxone (opioid antagonist) and yohimbine (alpha(2)-adrenoceptor antagonist) to probe receptor involvement.
- Repeated administration of agonists to evaluate effects on basal GH levels, pituitary GH content, and subsequent GH responses.
Main Results:
- Both clonidine and FK 33-824 increased plasma GH levels, with FK 33-824 showing a significantly greater effect.
- Yohimbine partially counteracted the FK 33-824-induced GH rise, suggesting an interaction between the systems.
- Repeated clonidine administration increased basal GH and pituitary GH content, enhancing the response to FK 33-824 but not to further clonidine.
- Repeated FK 33-824 administration enhanced GH response to both FK 33-824 and GH-releasing hormone, without affecting basal GH or pituitary content.
Conclusions:
- The GH-releasing effect of opioid peptides involves both adrenergic and extra-adrenergic components in rat pups.
- Opioid receptor stimulation does not induce GH synthesis, down-regulation, or tolerance, unlike short-term alpha(2)-adrenoceptor stimulation.
- Short-term opioid stimulation sensitizes to subsequent opioid challenges but does not affect alpha(2)-adrenergic challenges.
Abstract:
Abstract Functional interrelationships between hypothalamic adrenergic and opioid systems were studied in 10-day-old male and female rats. Either clonidine (150 mug/kg, sc), an alpha(2)-adrenoceptor agonist, or FK 33-824 (1 mg/kg, sc), a synthetic analog of met-enkephalin, increased plasma growth hormone (GH) levels, the increment being significantly higher with FK 33-824 than with clonidine. Pharmacologic blockade of opioid receptors with naloxone (5 mg/kg, sc) did not modify either basal GH levels, or the GH response to clonidine, whereas blockade of alpha(2)-adrenoceptors with yohimbine (2.5 mg/kg, sc) reduced basal GH levels and partially counteracted the FK 33-824-induced GH rise. Clonidine (150mu/kg, sc, twice daily) administered from postnatal day 5 to 9, increased basal GH levels and pituitary GH content. In these pups, acute administration of clonidine failed to further release GH, but the GH response to acute administration of FK 33-824 was significantly enhanced. A 5-day treatment with FK 33-824 (1 mg/kg, sc, twice daily), neither modified basal GH levels, nor pituitary GH content. Under these conditions, the in vivo GH response to an FK 33-824 challenge was significantly enhanced, and the response to clonidine was preserved. Pituitaries from FK 33-824-pretreated rats were hyperresponsive to GH-releasing hormone (10(-7) M). In summary, our data indicate that in rat pups: 1) two separate components i.e. one adrenergic, the other extra-adrenergic, subserve the GH-releasing effect of opioid peptides; 2) in contrast to short-term stimulation of alpha(2)-adrenoceptors, stimulation of opioid receptors does not trigger GH synthesis or induce down-regulation or tolerance; 3) short-term opioid stimulation does not affect an alpha(2)-adrenergic challenge, but sensitizes to an opioid challenge.
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