Activation of GABA receptors in the hypothalamus stimulates secretion of growth hormone and prolactin

Willoughby, John O.; Jervois, P.M.; Menadue, Margaret; Blessing, W.W.

doi:10.1016/0006-8993(86)90400-2

Cited by 54 publications

(32 citation statements)

References 27 publications

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“…Diffusion of opioids from the MBH to affect median eminence somatostatin or G R F terminals could also occur at higher doses, but injections do appear to spare the median eminence (36). We have previously shown that injections of muscimol in the PO/ AHA, but not in the MBH, stimulate G H secretion (36). and the reverse is true for serotonin (37), indicating that independent effects are observed after injections in either site.…”

Section: Methodsmentioning

confidence: 97%

“…Injections described below were made using 30 gauge injection needles inserted through the guide cannulae until they reached the skull. The level of the injection needles ensured that the opening of the needles was 0.5 mm above the (36)(37)(38).…”

Section: Methodsmentioning

confidence: 99%

“…The general locations of such injections as demonstrated using 0. I % horseradish peroxidase have been published previously (36).…”

Section: Tyr-d-ala-gly-(me)phe-gly-ol (Dago) [D-pend-penlenkephalinmentioning

confidence: 99%

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Intrahypothalamic Mu‐, not Delta‐ or Kappa‐Opioid Receptor Activation Causes Growth Hormone Secretion

Willoughby¹,

Kapoor²,

Mackenzie³

1991

J Neuroendocrinology

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Key words: growth hormone, mu-, kappa-and delta-opioid receptors, basal and anterior hypothalamus. AbstractThe possible effects of opioid receptor agonists on growth hormone (GH)-releasing factor or somatostatin neurons were examined by measuring the effects of localized intracerebral injections of mu-, delta-and kappa-selective agonists on GH secretion, Serial GH concentrations were measured in plasma in unanaesthetized male rats chronically prepared with venous and intracerebral cannulae, before and after treatment with bilateral intracerebral injections of opioid agonists in the preoptic anterior hypothalamic area and medial basal hypothalamus.In the medial basal hypothalamus, injections of the mu-agonist DAGO (Tyr-D-Ala-Gly-(Me)Phe-Gly-ol) caused dose-responsive increases in GH, the maximally effective dose being 0.001 nmoles. Injection of 10,000-fold higher doses of the delta-agonist DPDPE ([D-Pen,D-Penlenkephalin) and the kappa-agonist U50,488H were also effective in stimulating GH secretion. In the preoptic anterior hypothalamic area, DAGO caused dose-responsive increases in GH, the maximally effective dose being 0.01 nmoles. U50,488H was ineffective at 1,000-fold higher doses while DPDPE was effective at 100-to 1,000-fold higher doses.We conclude that hypothalamic mu-opioid receptor activation on or near somatostatin or GH-releasing factor neurons causes GH secretion, Opioids capable of acting on other opioid receptors may also stimulate GH secretion, though only at doses that seem likely to affect mu-receptors.The phenomenon of pulsatile growth hormone (GH) secretion is recognized to be a consequence of the net rhythmic stirnulatory action of somatostatin and GH-releasing factor (GRF) at the somatotroph (1-3). Somatostatin-and GRF-containing neurons are located in the periventricular preoptic/anterior hypothalamic area (PO/AHA) and arcuate nucleus in the medial basal hypothalamus (MBH), respectively (4-8). It has seemed probable from systemic and intracerebroventricular pharmacological studies that GH-regulating neurons are potently affected by opiates which usually cause marked stimulation of G H secretion. It has not clearly been demonstrated whether opioids act on somatostatin or G R F neurons or both. The present study uses a functional approach to determine possible actions of opioid receptor agonists on somatostatin-or GRF-containing neurons by measuring the effects on G H secretion of direct intrahypothalamic microinjections of opioid receptor agonists in the PO/AHA or MBH. The ligands we used in these experiments were highly selective for their receptor subtypes as shown by James and Goldstein (9), Tyr-D-Ala-Gly-(Me)PheGly-ol (DAGO) being 130 times more selective for mu than delta sites and 170 times more selective for mu than kappa. Similarly, [D-Pen,D-Penlenkephalin (DPDPE) is more selective for deltathan mu-(780 times) or kappa-receptors (430 times) and US0,488H is more selective for kappa-than mu-(1,300 times) o r delta-receptors (12,000 times) (9). Results P O / A H A injectionsRinger injec...

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Section: Methodsmentioning

confidence: 97%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Intrahypothalamic Mu‐, not Delta‐ or Kappa‐Opioid Receptor Activation Causes Growth Hormone Secretion

Willoughby¹,

Kapoor²,

Mackenzie³

1991

J Neuroendocrinology

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“…They were permitted free access to food and water and maintained on a 12 h lightdark cycle (lights on at 0700h) at an ambient temperature of 23°C. Intrahypothalamic injection and blood sampling procedures have been used extensively in previous studies and have been described in detail (12). Animals were anaesthetized with pentobarbitone (60 mg/kg, ip) and were prepared with a chronic indwelling right atrial catheter.…”

Section: Methodsmentioning

confidence: 99%

“…GH secretion is stimulated by a reduction in somatostatin release and sustained or increased G R F release (3)(4)(5). In stimulating GH, muscimol is presumed to act directly on somatostatin neurons because the latter have a GABA input (13) which, when activated, would inhibit somatostatin release and thereby allow secretion of GH (12). Possible augmentation of GRF neuronal activity by muscimol could also occur, possibly via inhibition of inhibitory neurons projecting from the PO/AHA t o GRF neurons, or via diminished inhibition of GRF terminals by somatostatin terminals a t the median eminence.…”

Section: Fig 3 (A) Mean (K Sem) Growth Hormone (Gh) Concentrations Inmentioning

confidence: 99%

Activation of Hypothalamic Gamma‐Aminobutyric Acid Receptors Resets the Pendulum of the Growth Hormone Clock

Willoughby¹,

Kapoor²

1990

J Neuroendocrinology

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Plasma levels of growth hormone in male rats exhibit a n ultradian rhythm having a periodicity of 3 to 4 h , bursts of growth hormone being separated by troughs when growth hormone secretion ceases. To determine if neurons in the vicinity of somatostatin neurons in the preopticlanterior hypothalamic area participate in the generation of t h e rhythm, we temporarily inhibited this region with injections of the y-arninobutyric acid agonist, muscimol, in unanaesthetized rats previously prepared with a venous catheter and stereotaxically implanted intracerebral guide tubes. The injection resulted in an immediate burst of growth hormone release, followed by a trough period and another growth hormone burst, 3.4k0.1 h later. The induction of a trough and synchronization of growth hormone bursts was not reproduced by a burst of intravenously injected exogenous growth hormone a t least as large as the first burst initiated by muscimol. These findings indicate that, in the short term, the ultradian rhythm is independent of growth hormone feedback and provide the first evidence that structures in the anterior hypothalamus receiving a y-aminobutyric acid input a r e an important component of the neural generator of the ultradian rhythm of growth hormone.

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GABA and glutamate in mating‐activated cells in the preoptic area and medial amygdala of male gerbils

Simmons

Yahr

2003

J of Comparative Neurology

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The posterodorsal medial amygdala (MeApd), the posterodorsal preoptic nucleus (PdPN), and the medial cell group of the sexually dimorphic preoptic area (mSDA) contain cells that are activated specifically at ejaculation as assessed by Fos expression. The mSDA also expresses Fos early in the mating context. Because little is known about the neurotransmitters of these activated cells, the possibility that they use gamma-aminobutyric acid (GABA) or glutamate was assessed. Putative glutamatergic cells were visualized with immunocytochemistry (ICC) for glutamate and its neuron-specific transporter. Their distributions were compared with those of GABAergic cells visualized with ICC for the 67-kDa form of glutamic acid decarboxylase (GAD(67)) and in situ hybridization for GAD(67) messenger RNA (mRNA). Colocalization of Fos and GAD(67) mRNA in recently mated males indicated that half of the activated cells in the PdPN, mSDA, and lateral MeApd are GABAergic. Colocalization of Fos and glutamate suggested that a quarter of the activated mSDA and lateral MeApd cells are glutamatergic. The PdPN does not appear to have glutamatergic cells. In the lateral MeApd, the percentage of activated cells that are GABAergic (45%) matches the percentage that project to the principal part of the bed nucleus of the stria terminalis (BST; 43%), and the percentage likely to be glutamatergic (27%) matches the percentage projecting to the mSDA (27%). The latter could help to trigger ejaculation. The distribution of GABAergic and putative glutamatergic cells in the caudal preoptic area, caudal BST, and medial amygdala of male gerbils is also described.

show abstract

Activation of GABA receptors in the hypothalamus stimulates secretion of growth hormone and prolactin

Cited by 54 publications

References 27 publications

Intrahypothalamic Mu‐, not Delta‐ or Kappa‐Opioid Receptor Activation Causes Growth Hormone Secretion

Intrahypothalamic Mu‐, not Delta‐ or Kappa‐Opioid Receptor Activation Causes Growth Hormone Secretion

Activation of Hypothalamic Gamma‐Aminobutyric Acid Receptors Resets the Pendulum of the Growth Hormone Clock

GABA and glutamate in mating‐activated cells in the preoptic area and medial amygdala of male gerbils

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