Eicosanoids and the hypothalamo-pituitary axis.
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Animals↗
Biomedical subjects
J C Buckingham
Publications and source records attributed to J C Buckingham.
Effect of estradiol and tamoxifen on GnRH self-priming in perifused rat adenohypophysial cells.
Columns of enzymatically dispersed rat pituitary cells have been used to examine the effects of estradiol and the estrogen receptor antagonist, tamoxifen, on the responsiveness of the gonadotropes to repeated challenges with GnRH. Synthetic GnRH stimulated readily the release of LH from the pituitary cells. When challenged repeatedly with the same submaximal dose (8 nmol/l) of the releasing hormone, cells from animals in diestrus 2 or pro-estrus, like those from juvenile rats, showed a marked progressive increase in their sensitivity, but those from rats in estrus or diestrus 1 did not. Adenohypophysial cells removed from adult rats ovariectomized 14 days previously also failed to exhibit sensitization even when estradiol-17 beta (1 and 10 nmol/l) was included in the perifusion fluid. However, those from ovariectomized rats treated with appropriate doses of the steroid (1.5 microgram/day sc for 14 days or 5 micrograms sc 22 h before decapitation) did. The capacity of pituitary cells from intact rats to exhibit priming on the anticipated day of pro-estrus was unaffected by the administration of the estrogen receptor antagonist, tamoxifen (700 micrograms/100 g sc on the morning of diestrus 1 and 24 h later). Similarly, addition of tamoxifen (1 mumol/l) to the incubation medium failed to influence the capacity of pituitary cells from juvenile rats to exhibit priming in vitro. The results support the concept that the ability of GnRH to 'prime' the gonadotropes is dependent on estradiol and indicate that the exposure of the hypothalamo-pituitary complex to critical levels of estradiol prior to autopsy is necessary for the gonadotropes to retain their capacity to exhibit priming in vitro.
Animals↗
Effects of selective opioid-receptor blockade on the hypothalamo-pituitary-adrenocortical responses to surgical trauma in the rat.
Opioid substances have been shown to stimulate and depress the secretion of ACTH in the rat. Their opposing actions appear to be mediated in part by specific receptors in the hypothalamus which influence the secretion of corticotrophin-releasing factor (CRF). In an attempt to determine the physiological role of these receptor systems, experiments were carried out in which the plasma ACTH and serum corticosterone concentrations were determined before and after stress in rats treated s.c. with selective antagonists of mu-(naloxone, naltrexone), delta-(ICI 174864) and kappa-(MR2266) opioid receptors. Neither naloxone (25-100 micrograms/100 g) nor naltrexone (50 micrograms/100 g) influenced the resting plasma ACTH or serum corticosterone concentrations. However, both inhibited (P less than 0.01) the secretion of the two hormones elicited normally by surgical stress (laparotomy under ether anaesthesia). ICI 174864 (30-100 micrograms/100 g) also had little effect on resting hypothalamo-pituitary-adrenocortical (HPA) activity but, at the highest dose, it caused a small (P less than 0.05) potentiation of the response to surgery. In contrast, MR2266 (150-300 micrograms/100 g) produced marked activation of the HPA system and not only stimulated the resting secretion of ACTH and corticosterone but also potentiated and prolonged the HPA response to stress. The results suggest that mu- and kappa-opioid receptors mediate opposing actions of endogenous opioid peptides, both of which may be physiologically important in the regulation of CRF release.
Adrenocorticotropic Hormone↗
Opioid binding sites in the fish brain: an autoradiographic study.
Cryostat sections of trout brains were incubated with tritiated opioid ligands (5 nM [3H]etorphine or 4 nM D-[3H]Ala2, Met5 enkephalinamide) with the initial aim of locating opioid binding sites associated with the hypothalamo-pituitary axis. Naloxone-displaceable binding was observed in all regions of the brain, with a density ranking order of cerebellum greater than telencephalon greater than optic tectum greater than hypothalamus greater than brain stem greater than pituitary gland. Within the hypothalamus and pituitary gland binding was unexpectedly low, apart from a slightly enhanced binding anteriorly in the preoptic region and posteriorly associated with presumptive sensory fibres. A similar distribution of opioid binding sites was seen in the eel and lamprey brain. The high level of opioid binding in the cerebellum permitted a tentative identification of opioid subtypes using [3H]etorphine binding to membrane preparations from trout cerebellum. Scatchard analysis indicated the presence of a single class of high-affinity binding sites with a density of 0.38 pmol/mg protein and affinity constant (KD) of 2.6 nM. Displacement by unlabelled ligands suggested the existence of mu and/or kappa receptors.
Anguilla↗
Hypothalamo-pituitary-interrenal responses to opioid substances in the trout. I. Effects of morphine on the release in vitro of corticotrophin-releasing activity from the hypothalamus and corticotrophin from the pituitary gland.
The effects of morphine and naloxone on the secretion in vitro of corticotrophin (ACTH) and and corticotrophin-releasing factor (CRF) by the pars distalis and hypothalamus, respectively, have been studied in the trout. The spontaneous in vitro secretion of corticotrophin by the pars distalis is depressed significantly by the addition of high concentrations of morphine (10(-6)-10(-7) mol/litre) to the incubation medium. The effect is naloxone reversible. Morphine does not influence the response of the pituitary tissue to exogenous CRF41, suggesting that the inhibitory influence of the opiate is exerted primarily on the CRF nerve terminals within the pars distalis and not on the corticotrophs. At considerably lower concentrations (10(-10)-10(-8) mol/litre) morphine stimulates the release of CRF from the isolated trout hypothalamus in vitro. Its effects are dose-dependent and antagonized by naloxone. The results suggest that two anatomically and pharmacologically distinct populations of opioid receptors mediate opposing actions of morphine on the hypothalamo-pituitary-corticotrophic system in the trout.
Adrenocorticotropic Hormone↗
Hypothalamo-pituitary-interrenal responses to opioid substances in the trout. II. Effects of morphine and D-Ala2, Met5-enkephalinamide on plasma cortisol titres in vivo.
The influence of morphine, D-Ala2, Met5-enkephalinamide (DALA), and naloxone on plasma cortisol titres has been studied in vivo in fingerling and adult trout. The responses were complex and variable. A single ip injection of morphine or DALA into fingerlings usually resulted in a rise in plasma cortisol after 0.5 hr followed by a fall below control values within 2 hr. In similar experiments with adult trout, only an inhibitory effect was observed. Naloxone reduced the rise in plasma cortisol following saline injection, but only when the hypothalamo-pituitary-interrenal response was intense. The antagonist also blocked the morphine-induced rise in cortisol secretion. Prolonged morphine treatment diminished both the postinjection and stress-induced secretion of cortisol in adult fish. Morphine had no effect on the spontaneous or ACTH-induced secretion of cortisol by interrenal tissue incubated in vitro. The results support the concept of inhibitory and stimulatory sites of action by opiates and opioid substances on the hypothalamo-pituitary-interrenal axis. These findings are discussed with reference to the action of morphine on hypothalamic and pituitary tissue of the trout in vitro and with the opioid control of hypothalamo-pituitary-adrenal function in mammals.
Adrenocorticotropic Hormone↗
Interrelationships of opioidergic and adrenergic mechanisms controlling the secretion of corticotrophin releasing factor in the rat.
The effects of morphine and naloxone on hypothalamo-pituitary-adrenocortical (HPA) activity and blood pressure were studied in rats in which adrenergic transmission had been impaired pharmacologically. The alpha 1-adrenoceptor antagonist, prazosin and the tyrosine hydroxylase inhibitor, alpha-methyl-para-tyrosine (alpha-MPT), increased the hypothalamic corticotrophin releasing factor (CRF) content and the plasma corticotrophin (ACTH) concentration and exaggerated the HPA response to stress. In addition, the spontaneous secretion of CRF by hypothalami in vitro was increased by alpha-MPT-treatment. Morphine enhanced the basal and stress-induced activity of the HPA system in vivo. It also stimulated the secretion of CRF by hypothalami in vitro. Naloxone did not affect resting HPA activity but reduced markedly the stress-induced release of corticotrophin. The effects of morphine and naloxone on the HPA axis, in vivo, were reduced by pretreatment with alpha-MPT and prazosin, respectively. The HPA responses could not be correlated with the changes in blood pressure which the drugs caused. The results suggest that opioid substances stimulate HPA activity by depressing the activity of the adrenergic pathways which inhibit the secretion of CRF.
Adrenocorticotropic Hormone↗
Vasopressin receptors influencing the secretion of ACTH by the rat adenohypophysis.
The effects of selective agonists and antagonists of type 1 (V1) and type 2 (V2) vasopressin receptors on the secretion of ACTH in vitro by segments of adenohypophysial tissue and in vivo in rats pretreated with pentobarbitone and chlorpromazine were studied in the presence and absence of the 41 amino acid-containing peptide, corticotrophin-releasing factor-41 (CRF-41). The non-selective vasopressin receptor agonist, arginine vasopressin (AVP) and the V1-receptor agonist, felypressin caused dose-related increases in ACTH release in vivo and in vitro but the V2-receptor agonist, desmopressin was only weakly active in this respect. Their actions in vitro were antagonized competitively by the V1-receptor antagonist, d(C2H5)2-AVP, but were unaffected by the V2-receptor antagonist, d(CH2)5-D-Iso2-Thr4-AVP. Arginine vasopressin, felypressin and desmopressins in concentrations considerably lower than those necessary to elicit directly the release of ACTH, potentiated, in a dose-related manner, the activity of CRF-41 in vitro. The potentiating effects were not antagonized by the V2-receptor antagonist or by low concentrations of the V1-receptor antagonist. At a higher concentration, the V1-receptor antagonist reduced, but did not abolish, the potentiating effects of AVP and its analogues. However, at this concentration, it also exhibited weak intrinsic activity and, like the agonists, potentiated the response to CRF-41. The results suggest that the direct effect of AVP on ACTH release is mediated by V1-like receptors. The vasopressin receptors involved in the potentiation of CRF-41 activity appear to be different.
Adrenocorticotropic Hormone↗
A role for leucocytes in the control of adrenal steroidogenesis?
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Adrenal Glands↗
Confined spaces--a case for ventilation.
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Accident Prevention↗
Effects of chronic administration of melanin-concentrating hormone on corticotrophin, melanotrophin, and pigmentation in the trout.
This paper reports the effects of salmonid melanin-concentrating hormone (MCH), administered via an Alzet minipump, on pigmentation and secretion of pituitary melanotrophin (MSH) and corticotrophin (ACTH) by black-adapted, adult rainbow trout. The drug induced melanin concentration in the skin melanophores and prevented melanogenesis. Both the cytological appearance of the pituitary pars intermedia and determinations of plasma alpha-MSH suggest that MCH prevented the increase in secretory activity of the melanotrophic cells seen normally in black-adapted trout. Resting plasma cortisol titres were similar in all groups of fish but anterior pituitary glands taken from stressed, MCH-treated fish released less ACTH in vitro than those from corresponding saline-treated fish.
Adrenocorticotropic Hormone↗
Stimulation and inhibition of corticotrophin releasing factor secretion by beta endorphin.
The influence of beta-endorphin on the secretion of corticotrophin releasing factor (CRF) by isolated rat hypothalami in vitro was studied. beta-Endorphin (10(-11)-10(-10) M) caused dose-related increases in the CRF contents of the hypothalami and of the medium in which they were incubated. Its effects were antagonized by naloxone (10(-8)-10(-7) M). In contrast, in higher concentrations (10(-7) - 10(-5) M), it reduced, in a dose-dependent manner, both the spontaneous release of CRF from the hypothalami and the release which normally occurred in response to acetylcholine, 5-hydroxytryptamine, morphine, met-enkephalin and leu-enkephalin. The inhibition of CRF release was associated with a rise in the tissue content of the hormone and was not blocked readily by naloxone. The results support the concept that opioid substances may be involved in the control of hypothalamo-pituitary-adrenocortical function.
Acetylcholine↗
Effects of naloxone on hypothalamo-pituitary-adrenocortical activity in the rat.
The influences of morphine and naloxone on hypothalamo-pituitary-adrenocortical (HPA) function were studied in the rat to investigate further the role of opioidergic mechanisms in the control of the secretion of corticotrophin and its hypothalamic releasing factor (CRF). Morphine not only caused rises in hypothalamic CRF content and plasma ACTH concentration but also potentiated the HPA response to stress. Its effects were antagonized by naloxone which, when given alone, did not influence basal plasma concentrations of ACTH and corticosterone but which inhibited, in a dose-dependent manner, the release of both of these hormones which normally occurs in response to stress. Naloxone also attenuated the exaggeration in stress-induced HPA activity but did not affect the increases in plasma ACTH concentration which followed adrenalectomy. The findings suggest that opioidergic mechanisms may be involved in the regulation of the HPA response to stress.
Adrenalectomy↗
Pharmacological characterization of opioid receptors influencing the secretion of corticotrophin releasing factor in the rat.
The effects of selective agonists and antagonists of opioid receptors on the secretion of corticotrophin releasing factor (CRF) by isolated rat hypothalami in vitro were studied. Morphine (10(-8)-10(-6) M) and the mu-opioid receptor agonists, FK33-824CH (10(-8)-10(-6) M) and Tyr-D-Ala-Gly-MePhe-NH(CH2)2OH (10(-8)-10(-6) M), caused dose-related increases in the release of CRF from isolated hypothalami. The kappa-opioid receptor agonist, U50,488 (10(-8)-10(-6) M), was also weakly active in this respect but the delta-opioid receptor agonist, (D-Pen2,D-Pen5)-enkephalin (2 X 10(-10)-2 X 10(-7) M), was not. The stimulatory actions of morphine and Tyr-D-Ala-Gly-MePhe-NH(CH2)2OH on CRF release were antagonized by naloxone (10(-8) M) and by the mu/delta-opioid receptor antagonist, beta-funaltrexamine (beta-FNA, 10(-9) M), but not by the delta-opioid receptor antagonist, ICI-154129 (5 X 10(-6) M). The effects of U50,488 on CRF release were unaffected by either beta-FNA or ICI-154129 but were antagonized by high doses of naloxone (10(-6) M). The results suggest that both mu- and kappa-opioid receptors are involved in the stimulation of CRF secretion but that delta-opioid receptors are not important in this respect.
Animals↗
Changes in the responsiveness of perifused rat adenohypophysial cells to repeated stimulation with luteinizing hormone releasing hormone.
The ability of luteinizing hormone releasing hormone (LRH) to stimulate the release of luteinizing hormone (LH) from columns of enzymatically dispersed perfused adenohypophysial cells is being used to study the mechanisms controlling the secretion of LH. LRH stimulated the release in vitro of LH from columns of rat pituitary cells. However, when exposed repeatedly (1 pulse every 12 min) to the same submaximal dose (8 nmol/l) of LRH the cells always exhibited a marked progressive increase and subsequent decrease in their responsiveness. Similar effects occurred when the interval between pulses was extended to 20, 30 or 45 min. The enhanced responsiveness of the cells was prevented by the inclusion of protein synthesis inhibitors, cycloheximide or puromycin, in the perifusion fluid. Cells removed from rats ovariectomized 14 days previously also failed to exhibit increased responsiveness when stimulated repeatedly with LRH. LH secretion was also elicited by K+ (50 nmol/l), 8-bromoadenosine 3'-5'-cyclic monophosphate (8-Br-cAMP, 6 nmol/l), 8-bromoguanosine 3'-5'-cyclic monophosphate (8-Br-cGMP, 6 nmol/l) and a calcium ionophore (A23187, 40 mumol/l) but the responses to these secretagogues differed markedly from those to LRH for the tachyphylaxis which resulted from repeated exposure was not preceded by an increase in responsiveness. The decreased responsiveness to K+ developed in parallel with that to LRH. Diminished responses to the cyclic nucleotides and the Ca++ ionophore developed more rapidly, but the refractory cells responded readily to stimulation with LRH or K+.(ABSTRACT TRUNCATED AT 250 WORDS)
8-Bromo Cyclic Adenosine Monophosphate↗
Corticotrophin-like bioactivity in the pituitary gland and brain of the pacific hagfish, Eptatretus stouti.
The cytochemical bioassay for corticotrophin (ACTH) was used in an attempt to detect ACTH-like activity in the Pacific hagfish, Eptatretus stouti. Extracts of the pituitary gland and brain were active in this assay system but those of liver and skeletal muscles were not. The slopes of the dose-response lines of the pituitary extracts were less than those of the mammalian corticotrophin standard preparation but greater than those of the brain extracts. The results suggest that the corticotrophic factor in the hagfish differs from mammalian ACTH.
Adrenal Glands↗
Hypothalamo-pituitary responses to trauma.
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Adrenal Cortex Hormones↗
Peripubertal changes in the nature of LH.
Administration of pregnant mare serum gonadotrophin (PMSG) to peripubertal rats, aged 27 days, induces ovulation provided the animals weigh more than 60 g at the time of the injection. In an attempt to determine whether the apparent immaturity of the ovaries in smaller rats is associated with an inability of the pituitary gland to secrete LH, the biological and immunological properties of LH in peripubertal PMSG-treated rats were examined. A single injection of PMSG caused a marked hypersecretion of LH in rats aged 27 days. The LH in the plasma of rats weighing more than 60 g was active in both the radioimmunoassay and the cytochemical bioassay but that in smaller rats was active only in the former. Plasma from both groups of rats stimulated the release of testosterone from dispersed Leydig cells. Luteinizing hormone-releasing hormone stimulated the secretion, in vitro, of immunoreactive, cytochemically active LH by pituitary tissue from rats weighing over 60 g. The LH released in vitro from tissue from the smaller animals, like that in their plasma, was active in the radioimmunoassay but not in the cytochemical system. The results suggest that an abrupt change in the nature of LH occurs at puberty and that ovulatory cycles commence only when the pituitary gland secretes the adult form of LH with a full spectrum of biological activity.
Animals↗