Enkephalin analogues and naloxone modulate the release of growth hormone and prolactin - evidence for regulation by an endogenous opioid peptide in brain

Shaar, Carl J.; Frederickson, Robert C.A.; Dininger, N B; Jackson, Lisa R.

doi:10.1016/0024-3205(77)90415-5

Cited by 267 publications

(63 citation statements)

References 16 publications

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“…Recent in-vitro studies showed that continued exposure of pituitary cells to opioids could suppress basal LH output (Cacicedo & Sanchez-Franco, 1986;Blank et al, 1986;Chao et al, 1986) and GnRH-stimulated LH release (Blank et al, 1986;Chao et al, 1986). Others have found that neither naloxone nor opiate agonists had any effect on short-term LH secretion from rat hemipituitaries in vitro (Shaar et al, 1977;Cicero et al, 1979;Grandison et al, 1980;Wiesner et al, 1984). Morphine did not alter the LH response to GnRH pulses in stalksectioned monkeys (Ferin et al, 1982 (Simantov & Snyder, 1977;Atweh & Kuhar, 1983;Lightman et ai, 1983); but are not present in the anterior pituitary of the monkey (Wamsley et al, 1982) (Kalra, 1981) or injection of antisera to ß-endorphin or dynorphin into the mediobasal hypothalamus (Schulz et al, 1981 ) stimulates LH release.…”

Section: Introductionmentioning

confidence: 99%

Naloxone evokes large-amplitude GnRH pulses in luteal-phase ewes

Horton¹,

Cummins²,

Clarke³

1987

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Summary. Ewes were sampled during the mid-late luteal phase of the oestrous cycle. Hypophysial portal and jugular venous blood samples were collected at 5\p=n-\10min intervals for a minimum of 3 h, before i.v. infusions of saline (12 ml/h; N = 6) or naloxone (40 mg/h; N = 6) for 2 h. During the 2-h saline infusion 2/6 sheep exhibited a GnRH/LH pulse; 3/6 saline infused ewes did not show a pulse during the 6\p=n-\8-hportal blood sampling period. In contrast, large amplitude GnRH/LH pulses were observed during naloxone treatment in 5/6 ewes. The mean ( \ m=+-\ s.e.m.) amplitude of the LH secretory episodes during the naloxone infusion (1\m=.\07\ m=+-\ 0\m=.\11ng/ml) was significantly (P < 0\m=.\05) greater than that before the infusion in the same sheep (0\m=.\54 \ m=+-\0\m=.\15 ng/ml). Naloxone significantly (P < 0\m=.\005) increased the mean GnRH pulse amplitude in the 5/6 responding ewes from a pre-infusion value of 0\m=.\99\ m=+-\ 0\m=.\22pg/min to 4\m=.\39\ m=+-\1\m=.\10pg/min during infusion. This episodic GnRH secretory rate during naloxone treatment was also significantly (P < 0\m=.\05)greater than in the saline-infused sheep (1\m=.\53 \m=+-\0\m=.\28 pg/min). Plasma FSH and prolactin concentrations did not change in response to the opiate antagonist.Perturbation of the endogenous opioid peptide system in the ewe by naloxone therefore increases the secretion of hypothalamic GnRH into the hypophysial portal vasculature. The response is characterized by a large-amplitude GnRH pulse which, in turn, causes a large-amplitude pulse of LH to be released by the pituitary gland.

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Section: Introductionmentioning

confidence: 99%

Naloxone evokes large-amplitude GnRH pulses in luteal-phase ewes

Horton¹,

Cummins²,

Clarke³

1987

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“…Their evidence for this is: (1) that naltrexone administration reduces the serum levels of prolactin in intact rats and in rats with deafferentation of the hypothalamus; (2) that dopamine, but not naltrexone, reduces release of prolactin from pituitary halves in vitro; (3) that intrahypothalamic injection of naltrexone reduces, and of ß-endorphin increases, serum prolactin levels; (4) that after dopamine receptor blockade by haloperidol or depletion of dopamine stores by reserpine, serum prolactin levels are increased and that these elevated levels are undiminished by naltrexone. The observation that administration of an opiate antagonist alone reduces the serum concentration of prolactin has been confirmed by other groups who also showed that GH was similarly affected (Bruni, van Vugt, Marshall & Meites, 1977;Shaar et al, 1977). This is the most convincing evidence for a physiological role of endogenous opioid peptides in the tonic control of the release of GH and prolactin.…”

Section: Physiological Significance Of the Opioid Peptidesmentioning

confidence: 58%

“…Most attention has been directed towards growth hormone (GH) and prolactin and there is general agreement that the enkephalins and various enkephalin analogues and ß-endorphin, like morphine, produce increased release of both hormones and that these increases are inhibited by opiate antagonists, naloxone and naltrexone (see Cusan et al, 1977;Rivier, Vale, Ling, Brown & Guillemin, 1977;Shaar, Frederickson, Dininger & Jackson, 1977). There is one report of release of prolactin from cultured pituitary cells by enkephalin (Lien, Fenichel, Garsky, Sarantakis & Grant, 1976) but more recent evidence contradicts this and suggests that the release of both GH and prolactin by morphine and opioid peptides is not due to a direct action on the pituitary (Rivier et al, 1977;Shaar et al, 1977). Grandison & Guidotti (1977) and Guidotti & Grandison (1978) concluded that endogenous opioids control the release of prolactin by inhibiting dopaminergic mechanisms in the mediobasal hypo¬ thalamus.…”

Section: Physiological Significance Of the Opioid Peptidesmentioning

confidence: 99%

Opioid peptides and pituitary function

McKnight¹,

Kosterlitz²

1980

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“…These effects can be counteracted by the opiate antagonist naloxone. Although there are some observations indicating a direct action of opioid peptides on the anterior pituitary (6)(7)(8)(9), most of the findings suggest that they may exert their influence via the CNS (10)(11)(12)(13). Such a view is consistent with the presence of all three families of endogenous opioid peptides (proopiomelanocortin-derived endorphins, enkephalins and dynorphins) and opioid peptide receptors in the brain.…”

mentioning

confidence: 80%

Central Nervous System Sites of Action of an Enkephalin Analogue, (D‐Met², Pro⁵)‐Enkephalinamide, and Naloxone on the Secretion of Five Anterior Pituitary Hormones of Male Rats

Molnár

Marton

Halász

1990

J Neuroendocrinology

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Central nervous system sites of action of opioid peptides on pituitary hormone secretion were investigated. One nmol of an enkephalin analogue, (D-Met', Pros)-enkephalinamide, and 10 nmol of the opiate antagonist naloxone were injected into ten different regions of the brain of conscious male rats and their effect on the release of five anterior pituitary hormones tested. The injections were made through a special injection cannula which was inserted into the brain through a guide cannula fixed on the skull and implanted into the brain 5 to 7 days earlier. Both compounds injected into the medial septum, medial preoptic area and hypothalamic paraventricular nucleus affected prolactin, growth hormone and luteinizing hormone (LH) secretion. The enkephalin analogue stimulated prolactin and growth hormone and inhibited LH release. Naloxone induced the opposite effect. Drugs given into the hypothalamic ventromedial nucleus caused changes in plasma prolactin and growth hormone levels. Enkephalinamide increased and naloxone decreased plasma concentrations of both hormones. Administration of the compounds into the dorsal raphe area resulted in alterations of prolactin and LH release, the analogue caused elevation of prolactin and inhibition of LH release, whereas the opiate antagonist resulted in opposite changes. Only an LH response was obtained from the hypothalamic dorsomedial nucleus and a growth hormone response from the central amygdala. Also in these cases the enkephalin analogue decreased LH and elevated growth hormone plasma levels, and naloxone brought about a rise in LH and a diminution of growth hormone concentration. None of the regions were effective in inducing a clear-cut adrenocorticotrophin or follicle-stimulating hormone response. The parietal cortex, medial amygdala and the dentate gyrus were entirely ineffective sites. The findings suggest that in the brain there are multiple sites of action of opioids on pituitary trophic hormone secretion and the effective sites are not identical in terms of pituitary hormone response.4 large number of experimental data indicate (1-5) that opioid peptides affect secretion of pituitary trophic hormones. In general, it appears that they stimulate prolactin (PRL) and growth hormone (GH), inhibit the release of gonadotrophins, primarily of luteinizing hormone (LH), and elevate or depress plasma adrenocorticotrophin (ACTH) and thyrotroph hormone levels. These effects can be counteracted by the opiate antagonist naloxone. Although there are some observations indicating a direct action of opioid peptides on the anterior pituitary (6-9), most of the findings suggest that they may exert their influence via the CNS (10-13). Such a view is consistent with the presence of all three families of endogenous opioid peptides (proopiomelanocortin-derived endorphins, enkephalins and dynorphins) and opioid peptide receptors in the brain. The observations that opiate antagonists or opiate receptor blockcrs cause alterations in pituitary trophic hormone secretion suggest that en...

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Enkephalin analogues and naloxone modulate the release of growth hormone and prolactin - evidence for regulation by an endogenous opioid peptide in brain

Cited by 267 publications

References 16 publications

Naloxone evokes large-amplitude GnRH pulses in luteal-phase ewes

Naloxone evokes large-amplitude GnRH pulses in luteal-phase ewes

Opioid peptides and pituitary function

Central Nervous System Sites of Action of an Enkephalin Analogue, (D‐Met², Pro⁵)‐Enkephalinamide, and Naloxone on the Secretion of Five Anterior Pituitary Hormones of Male Rats

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Enkephalin analogues and naloxone modulate the release of growth hormone and prolactin - evidence for regulation by an endogenous opioid peptide in brain

Cited by 267 publications

References 16 publications

Naloxone evokes large-amplitude GnRH pulses in luteal-phase ewes

Naloxone evokes large-amplitude GnRH pulses in luteal-phase ewes

Opioid peptides and pituitary function

Central Nervous System Sites of Action of an Enkephalin Analogue, (D‐Met2, Pro5)‐Enkephalinamide, and Naloxone on the Secretion of Five Anterior Pituitary Hormones of Male Rats

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Central Nervous System Sites of Action of an Enkephalin Analogue, (D‐Met², Pro⁵)‐Enkephalinamide, and Naloxone on the Secretion of Five Anterior Pituitary Hormones of Male Rats