Intrahypothalamic action of corticotrophin-releasing factor (CRF) to inhibit growth hormone and LH release in the rat

Ono, Norihito; Lumpkin, Michael D.; Samson, Willis K.; McDonald, John K.; McCann, Samuel M.

doi:10.1016/0024-3205(84)90077-8

Cited by 157 publications

(57 citation statements)

References 15 publications

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“…We found to our surprise that injection of ovine CRF (oCRF) into the third ventricle decreases plasma growth hormone with a minimal effective dose of 0.1 nmol. A higher dose (1.0 nmol) also decreased plasma luteinizing hormone (LH) (4,5). In both instances, similar results have been obtained following lateral ventricular injection of the peptide (6, 7).…”

supporting

confidence: 70%

Ultrashort-loop positive feedback of corticotropin (ACTH)-releasing factor to enhance ACTH release in stress.

Ono¹,

Castro²,

McCann³

1985

Proc. Natl. Acad. Sci. U.S.A.

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Previous experiments have shown that intraventricular injection of ovine corticotropin (ACTH)-releasing factor (oCRF) in doses too low to elevate plasma ACTH by direct action on the pituitary does not lower plasma ACTH, suggesting that the peptide lacks a negative ultrashortloop feedback action to suppress its own release under resting conditions. The present study was performed to determine whether oCRF has any action to alter CRF release in stress.The peptide was injected into the third ventricle or external jugular vein of freely moving ovariectomized female rats 5 min prior to application of ether stress. When oCRF was injected into the third ventricle in doses of 500 pg (0.1 pmol) or less, there was no significant alteration in plasma ACTH prior to ether stress; however, there was a significantly enhanced increase in plasma ACTH 2 and 5 min after ether stress applied 5 min after intraventricular injection of oCRF at doses of 50 (0.01 pmol) or 150 pg (0.03 pmol). These results suggest that the peptide acts on structures adjacent to the third ventricle to augment stress-induced CRF release. To rule out the possibility that the sensitivity of the pituitary itself to CRF increases dramatically following stress, 10 or 100 ng of oCRF was injected i.v. These doses produced a significant dose-related increase in plasma ACTH at 2, 5, or 15 min. In other groups receiving the same doses of oCRF and ether stressed 5 mI later, plasma ACTH was significantly higher 2 or 5 min after ether stress when compared with plasma ACTH in etherstressed saline-injected animals. However, in contrast with the results of intraventricular injection of oCRF, the release of ACTH was no greater than that obtained by summing the independent effects of exogenous oCRF and the CRF released by stress. We conclude that CRF may have a positive ultrashortloop feedback action to enhance stress-induced ACTH release and that this enhancement is not due to increased sensitivity of anterior pituitary corticotrophs to CRF.Ultrashort-loop feedback of releasing hormones to alter their own release was postulated a number of years ago by Martini and co-workers (1). There now appears to be a number of examples of this type of interaction of peptides within the brain to alter their own release. The existence ofan ultrashortloop feedback mechanism by which somatostatin alters its own release has been suggested (2). Similarly, intraventricular injection of oxytocin appears to inhibit its own release (3).Consequently, we have looked for possible interactions of corticotropin (ACTH)-releasing factor (CRF) with other peptides in the hypothalamus. We found to our surprise that injection of ovine CRF (oCRF) into the third ventricle decreases plasma growth hormone with a minimal effective dose of 0.1 nmol. A higher dose (1.0 nmol) also decreased plasma luteinizing hormone (LH) (4, 5). In both instances, similar results have been obtained following lateral ventricular injection of the peptide (6, 7). Thus, it appears that the CRF neurons interact with those con...

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supporting

confidence: 70%

Ultrashort-loop positive feedback of corticotropin (ACTH)-releasing factor to enhance ACTH release in stress.

Ono¹,

Castro²,

McCann³

1985

Proc. Natl. Acad. Sci. U.S.A.

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“…Thus the sensitivity for the inhibitory effect of NPY on GH release was less than that for LH by at least a factor of 100; however, this threshold is not different from that of a number of other peptides that may have physiological effects on the release of hypothalamic factors controlling GH, such as corticotropinreleasing factor (16). In view of the localization of NPY cell bodies and terminals in hypothalamic areas that control GH release (17,18), this action may be exerted via a stimulation of somatostatin release, by an inhibition of GH-releasing factor release, or by a combination of these two actions.…”

Section: Resultsmentioning

confidence: 99%

Neuropeptide Y affects secretion of luteinizing hormone and growth hormone in ovariectomized rats.

McDonald¹,

Lumpkin²,

Samson³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

229

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Neuropeptide Y (NPY) has recently been localized in the rat hypothalamus. We have evaluated the effects of NPY on hypothalamic and pituitary function by injecting NPY into the third ventricle in vivo and by examining its action on perifused pituitary cells in vitro. Injection of NPY into the third ventricle of conscious ovariectomized rats led to a dramatic and highly significant reduction in plasma luteinizing hormone (LH) relative to pretreatment levels in these animals or to those of controls injected with physiological saline. Significant inhibition was obtained with doses ranging from 0.02 to 5.0 1Ag (4.7-1175 pmol) Neuropeptide Y (NPY) was isolated from porcine brain by Tatemoto and co-workers (1, 2). It contains 36 amino acids and displays marked sequence homology to avian and bovine pancreatic polypeptide (APP and BPP). NPY-like immunoreactivity has been localized throughout the brain (3, 4, t, t), and especially high concentrations (5, 6) have been measured in the hypothalamus of the rat and human by RIA. NPY appears to be located in certain brainstem noradrenergic and adrenergic nuclei that project to the hypothalamus and also in intrinsic hypothalamic neurons (3, 4, t, t (225-250 g) were bilaterally ovariectomized while they were under ether anesthesia, 3-5 weeks before implantation of a 3V cannula or before decapitation for collection of anterior pituitary glands. The animals were housed in group cages under controlled conditions of temperature (23-25°C) and illumination (lights on 0500-1900) and were provided food and water ad lib.Jugular Cannulation. Twenty-four hours prior to 3V injection of NPY or saline (0.9% NaCl), a cannula was inserted into the right external jugular vein by using an established procedure (7). On the day of the experiment, the cannula was connected to a longer flexible tube (PE-50, Clay Adams) containing heparin and saline. This system allowed rapid collection of blood samples (0.6 ml) and replacement of blood volume with 0.9% NaCl without disturbing the animal. Rats were acclimated to these conditions for at least 1 hr prior to 3V injection of NPY.Ventricular Injections and Blood Sampling. A stainless steel cannula (23 gauge) was implanted into the third ventricle 7-10 days before the experiment (8). Various doses of synthetic porcine NPY (lots 003778 and 004219, Peninsula Laboratories, Belmont, CA) or an equal volume (2 ,u) of diluent (0.9% NaCl) was injected into the third ventricle of conscious, unrestrained animals after withdrawal of a preinjection blood sample (0.6 ml) through the jugular cannula. This blood sample was designated the 0-min sample and subsequent samples were obtained at various times after 3V injection. Samples were stored on ice and later spun at low speed at 4°C, the supernatant was removed, and plasma was divided into aliquots immediately or stored frozen for RIA to determine the concentrations of luteinizing hormone (LH) and growth hormone (GH) as well as follicle-stimulating hormone (FSH) in one experiment.Anterior Pituitary Cell Perif...

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“…The mechanisms responsible for the siress-induced suppression of gonadotrophin release are not clearly understood but data from a number of in vitro and in vivo studies suggest that CRF-41 may be important in this respect. Its site of action appears to be within the hypothalamus (6)(7)(8)(9)(10) and may involve an increase in the a-endorphinergic inhibitory tone to the gonadotrophin-releasing hormone (GnRH) neurons (1 1-13). Observations that CRF-41 and AVP are colocalized within the parvocellular neurons of the paraventricular nucleus (14) and that the two neuropeptides are co-secreted in response to certain stressors (15) raise the possibility that AVP may also contribute to the inhibition of luteinizing hormone (LH) release during stress.…”

mentioning

confidence: 99%

A Role for Vasopressin in the Stress‐Induced Inhibition of Gonadotrophin Secretion: Studies in the Brattleboro Rat

Cover

Laycock

Gartside

et al. 1991

J Neuroendocrinology

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The effects of stress on the secretion of adrenocorticotrophin, corticosterone and luteinizing hormone (LH) in rats congenitally lacking hypothalamic vasopressin (Brattleboro rats) and in normal controls of the parent strain (Long Evans) have been compared in an attempt to examine the role of vasopressin in the stress-induced depression of gonadotrophin secretion. In the Long Evans rats, stress (0.6 mg/100 g histamine, ip) initiated, within 5 and 20 min respectively, significant (P< 0.01, Student's t-test) increases in the plasma adrenocorticotrophin and corticosterone concentrations. It also caused a reduction in the serum LH concentration which was maximal a t 5 min. By contrast, in the vasopressin deficient Brattleboro rats, stress had no effect on the serum LH concentration and produced only modest increases in pituitary adrenocortical activity compared with those in Long Evans controls. Pretreatment of both Long Evans and Brattleboro rats with dexamethasone (20 pg1100 g ip, daily for 3 days) effectively abolished the pituitary-adrenal response to stress. The steroid treatment also prevented the stress-induced suppression of LH in the Long Evans rats; indeed, these animals, unlike the vehicle-treated controls, exhibited a rise in serum LH concentration within 5 min of exposure to stress. Stress did not affect the serum LH concentrations in steroid-treated Brattleboro rats. The results confirm previous reports that vasopressin is required for the full expression of the pituitary-adrenocortical response stress. They also provide novel evidence which suggests that vasopressin released in stress contributes to the impairment of gonadotrophin secretion.Stress produces a number of endocrinological changes including activation of the hypothalamo-pituitary-adrenal (HPA) axis and impairment of reproductive function ( I , 2). The stress-induced hypersecretion of adrenocorticotrophin (ACTH) is initiated primarily by two hypothalamic neuropeptides, the 41-amino-acid corticotrophin-releasing factor (CRF-4 1) and arginine vasopressin (AVP). AVP alone is a relatively weak secretagogue (3) but it potentiates markedly the more powerful actions of CRF-41 at the pituitary level (4, 5). The mechanisms responsible for the siress-induced suppression of gonadotrophin release are not clearly understood but data from a number of in vitro and in vivo studies suggest that CRF-41 may be important in this respect. Its site of action appears to be within the hypothalamus (6-10) and may involve an increase in the a-endorphinergic inhibitory tone to the gonadotrophin-releasing hormone (GnRH) neurons (1 1-13). Observations that CRF-41 and AVP are colocalized within the parvocellular neurons of the paraventricular nucleus (14) and that the two neuropeptides are co-secreted in response to certain stressors (15) raise the possibility that AVP may also contribute to the inhibition of luteinizing hormone (LH) release during stress. Accordingly, we have examined the effects of histamine stress on the release of LH and ACTH in rats with he...

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Intrahypothalamic action of corticotrophin-releasing factor (CRF) to inhibit growth hormone and LH release in the rat

Cited by 157 publications

References 15 publications

Ultrashort-loop positive feedback of corticotropin (ACTH)-releasing factor to enhance ACTH release in stress.

Ultrashort-loop positive feedback of corticotropin (ACTH)-releasing factor to enhance ACTH release in stress.

Neuropeptide Y affects secretion of luteinizing hormone and growth hormone in ovariectomized rats.

A Role for Vasopressin in the Stress‐Induced Inhibition of Gonadotrophin Secretion: Studies in the Brattleboro Rat

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