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Biomedical subjects

S M McCann

Publications and source records attributed to S M McCann.

At least 217 records · Page 12Linked to original sources
PubMed1986

The effect of unilateral decortication on the patterns of pulsatile follicle stimulating hormone (FSH) and luteinizing hormone (LH) release and on mean plasma prolactin (Prl) levels in the ovariectomized rat.

Previous experiments have shown that unilateral decortication is followed by an elevation in FSH and LH secretion, but there has been no study of the rhythms of release of gonadotropins in these animals. Consequently, this study was undertaken to determine if there are alterations in the pulsations of gonadotropins following hemi-decortication and also to measure plasma Prl in these animals to determine if it might also be under the influence of extrahypothalamic pathways. Our results show an increased mean plasma LH in unilateral decorticate animals that occurred because of an increase in pulse frequency without a significant increase in pulse amplitude. Mean plasma FSH was also elevated significantly in unilaterally decorticate animals, but there was no significant change in pulse frequency or amplitude. The length of the interpulse interval for LH release secretion decreased in unilateral decorticate animals, whereas the length of the cycle of FSH secretion increased in this circumstance. The mean levels of Prl were reduced in unilateral decorticate animals. These changes indicate that unilateral removal of cortico-rhinencephalic structures has an excitatory influence on gonadotropin secretion mediated by an increased frequency of LH and decreased frequency of FSH pulsations in the castrate, while at the same time there is a lowering of plasma Prl, probably due to removal of excitatory cortico-rhinencephalic pathways.

Animals↗
PubMed1986

The effects of the cholecystokinin antagonist, proglumide, on gonadotropin release in the rat.

Since cholecystokinin had manifest effects on anterior pituitary hormone secretion following its intraventricular injection in ovariectomized rats, we have evaluated the effects of the cholecystokinin antagonist, proglumide, to assess the physiologic significance of CCK in the control of gonadotropin secretion. Conscious rats of either sex were used following implantation of third ventricular and/or intravenous cannulae for the administration of proglumide. Blood samples were drawn from conscious animals at various times after the injection of the compound. In castrate female rats proglumide produced a small but significant increase in plasma LH whether administered by the intravenous or intraventricular route at the lower dose of 10 or 2 micrograms, respectively. The higher doses of 10 micrograms injected intraventricularly or 100 micrograms, injected intravenously failed to affect LH levels in these animals. In contrast there was a much larger increase in plasma LH in castrate males following intraventricular or intravenous injection of the lower doses of proglumide. Even after the higher doses, there was a slight increase in levels of LH by either route of injection. The results indicate that in the castrate animal proglumide can elevate LH levels by either route of injection but that the response is greater in castrate males than females. The reduction in response with the higher doses may reflect an agonist activity of proglumide. By contrast proglumide had no effect on plasma FSH except for a slight elevation observed following the intravenous or intraventricular injection of the lower doses of the compound in castrate males. The results favor a physiologically significant role of CCK in control of LH release in the rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Beta-adrenergic agonists increase amplitude of LH release in orchidectomized rats.

The role of intravenously (iv) injected adrenergic agonists in the pulsatile secretion of luteinizing hormone (LH) was examined in unanesthesized, freely behaving, castrated male rats. The alpha 2-adrenergic receptor agonist, clonidine (25 micrograms/kg), and the alpha 1-adrenergic agonist, (-)-phenylephrine (12.5 micrograms/kg), did not significantly alter pulsatile release of LH. The physiological beta 2-adrenergic receptor agonist, (-)-epinephrine (2.5 micrograms/kg), significantly increased the mean plasma concentrations of plasma LH and the amplitude of the LH pulses over a period of 70 min. The specific beta 2-receptor agonist, salmefamol, significantly increased the mean plasma concentrations of LH and especially the average amplitude of LH pulses over 70-80 min in a dose-related fashion following the injection of doses from 25 to 125 micrograms/kg. The frequency of LH pulses was not significantly increased by either agonist at any of the doses employed. Salmefamol-induced increases in plasma LH could be prevented by the beta-adrenergic blocker, bornaprolol (FM-24), in a dose-related manner. When injected together with synthetic LH-releasing hormone (400 ng/kg), salmefamol (125 micrograms/kg) significantly increased the mean plasma concentrations of LH over 70 min compared with values in controls receiving LH-releasing hormone only. The data support the concept that beta-agonists act on their receptors in the pituitary to facilitate LH-releasing hormone-induced discharge of LH.

Adrenergic beta-Agonists↗
PubMed1986

Central administration of alpha-MSH antiserum augments fever in the rabbit.

alpha-Melanocyte-stimulating hormone (alpha-MSH) has a marked antipyretic action when given centrally or peripherally, and the concentration of this peptide within the septal region of the brain increases during fever. To assess the significance of endogenous central alpha-MSH in fever, antiserum was given to rabbits via a cannula implanted in the third cerebral ventricle. Each day for 3 days, the animals received 50 microliters of normal rabbit serum (NRS) or an equal volume of antiserum raised against alpha-MSH. Interleukin 1 (IL 1) was then injected intravenously to determine the effect of central immunoneutralization of alpha-MSH on the febrile response. Immunoneutralization markedly prolonged fever. The average rise in temperature and the area under the fever curve after IL 1 injection were also significantly increased. Antiserum treatment did not alter normal body temperature, and NRS had no effect on IL 1-induced fever. These results indicate that endogenous central alpha-MSH contributes to physiological limitation of fever and that the role of this peptide in temperature regulation is relevant to the febrile state but not to normothermia.

Animals↗
PubMed1986

Opioid kappa receptors and the secretion of prolactin (PRL) and growth hormone (GH) in the rat. I. Effects of opioid kappa receptor agonists bremazocine and U-50,488 on secretion of PRL and GH: comparison with morphine.

The effects of bremazocine and U-50,488, two selective opioid kappa receptor agonists, and the preferential mu receptor agonist morphine on the secretion of PRL and GH were compared in conscious male rats bearing permanent right atrial cannulae for serial blood sampling and drug delivery. All three opioids stimulated PRL secretion in a dose-related manner, but the kappa agonists differed from morphine in several respects. They were considerably more potent than morphine in triggering a PRL response, but were unable to elevate PRL levels to more than 100 ng/ml, whereas morphine, at the highest dose (4.5 mg/kg), induced an almost twice larger response. Also their PRL-releasing effect was inhibited more strongly by the preferential kappa receptor antagonist Mr-2266 than by naloxone, whereas Mr-2266 and naloxone, which are equipotent as antagonists of the mu receptors, were equipotent in suppressing the PRL-stimulating effect of morphine, a mu agonist. In a complete contrast to morphine, which effectively stimulated GH secretion, the kappa agonists had no effect on GH release at lower doses and suppressed it at higher doses. It is concluded that the PRL-releasing effect of the kappa agonists is mediated by the kappa receptors which may participate with the mu receptors in regulation of PRL secretion by opioids. The GH-inhibiting effect of the kappa agonists requires further clarification.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1986

Opioid kappa receptors and the secretion of prolactin (PRL) and growth hormone (GH) in the rat. II. GH and PRL release-inhibiting effects of the opioid kappa receptor agonists bremazocine and U-50,488.

An analysis of the GH release-inhibiting action of the opioid kappa receptor agonists bremazocine and U-50,488, established earlier, was attempted by testing the agonists against activation of GH secretion by morphine or clonidine in male rats bearing right atrial cannulae for serial blood sampling and drug delivery. Both kappa agonists inhibited the effect of subsequent administration of clonidine in a dose-related manner. Bremazocine was approximately ten times more potent than U-50,488, a ratio corresponding to the known affinities of the two compounds for the kappa receptors. The inhibiting action of bremazocine was more strongly reversed by the preferential kappa receptor antagonist Mr-2266 than by naloxone, neither of which interfered with the GH-stimulating effect of clonidine. Bremazocine, however, did not alter the activation of GH secretion by exogenous growth hormone releasing factor. Thus, the inhibiting effect of bremazocine and probably U-50,488 seems to be derived from stimulation of the kappa receptors which in turn activates a GH release inhibiting mechanism of unknown identify which, however, does not involve release of somatostatin. Both kappa agonists also inhibited the effect of morphine, but in this case U-50,488 was approximately hundred times less effective than bremazocine. Since bremazocine and U-50,488 are antagonists of the delta receptors, which seem to mediate the GH-releasing effect to morphine, their inhibiting effect in this instance may be related to this property rather than to an action on the kappa receptors. Bremazocine, but not U-50,488, was also highly effective in inhibiting stimulation of PRL secretion by morphine.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1986

On the presence of a nondopaminergic, peptidergic prolactin release-inhibiting factor in hypothalamic extracts of infantile rats.

Crude hypothalamic extracts prepared from brains of 1-day-old rats produced a dose-dependent inhibition of prolactin (Prl) release by adult male hemipituitaries, and to a lesser extent by hemipituitaries of adult ovariectomized (OVX), estrogen-primed rats. These extracts contained 6-fold lower levels of dopamine than adult hypothalami. The inhibitory effect of the adult hypothalamic extracts, contrary to infantile hypothalamic extracts could be blocked by spiroperidol. Digestion of the infantile hypothalamic extracts with pronase totally abolished their Prl release-inhibiting activity, indicating the peptidic nature of this inhibitory substance. In contrast to their effect on Prl release by hemipituitaries, infantile hypothalamic extracts stimulated Prl release from dispersed anterior pituitary cells of OVX estrogen-primed rats, pointing to the importance of estrogen in modulating prolactin release-inhibiting factor (PIF) activity and the possibility that the PIF receptor is trypsin-sensitive.

Age Factors↗
PubMed1986

Central administration of atrial natriuretic factor inhibits saline preference in the rat.

Atrial natriuretic factors (ANFs), produced in myocytes of mammalian atria, exert potent natriuretic and diuretic actions in the kidney as well as a variety of other actions coordinated to normalize extracellular fluid volume. Recently, ANF-like immunoreactivity has been detected in the hypothalamus of the rat, and central administration of ANF has been shown to block dehydration-induced water intake. We describe here the ability of 0.2 and 2.0 nmol atriopeptin III to inhibit saline intake when infused into the third ventricle of conscious, salt-depleted rats; an effect that was dose-related and long-lasting (24 h). These studies provide further evidence for a central nervous system action of ANF, which, together with its established renal and adrenal actions, might be an important feature of the coordinated physiological control of fluid volume.

Animals↗
PubMed1986

Evidence for a physiological role for oxytocin in the control of prolactin secretion.

The presence of oxytocin (OT) in neuronal elements of the external layer of the median eminence and in hypophysial portal plasma suggests a role for the peptide in the control of anterior pituitary function. We have reported previously that OT stimulates PRL release in vitro; therefore, we attempted to establish evidence for a physiological PRL-releasing role for OT. Plasma OT levels rose significantly just before the PRL surges occurring during a suckling stimulus in lactating rats (10 min after pup reinstatement vs. 15 min for PRL) and 48 h after estrogen injection in ovariectomized (OVX) rats (at 1200 h vs. 1300 h). Dispersed anterior pituitary cells harvested from lactating female rats and OVX estrogen-primed rats released PRL in a specific, significant, and dose-related fashion when perifused in vitro with incubation medium containing 10(-7)-10(-9) M OT, doses similar to levels found previously in hypophysial portal plasma. Infusion of antiserum specific for OT into lactating females before pup reinstatement and into estrogen-primed OVX rats 2 h before the expected release of endogenous OT delayed and significantly reduced subsequent PRL surges compared to levels in saline-or normal rabbit serum-infused rats; however, PRL release was not completely abolished. These data indicate that OT plays a physiological role in the hypothalamic control of PRL secretion and further suggest the importance of multiple factors in coordinated regulation of PRL release.

Animals↗
PubMed1986

Interaction of alpha-melanocyte-stimulating hormone with beta-endorphin to influence anterior pituitary hormone secretion in the female rat.

The interaction of alpha MSH and beta-endorphin on the secretion of PRL, GH, and LH was determined in the ovariectomized rat. The potent stimulatory effect on PRL release of injection of 20 ng (5.8 pmol) beta-endorphin into the third cerebral ventricle was completely blocked by 100 ng (60 pmol) alpha MSH. The same dose of alpha MSH partially blocked the effect of 150 ng (44 pmol) beta-endorphin on PRL secretion. Intraventricular injection of either 20 ng beta-endorphin or 100 ng alpha MSH had no effect by itself on plasma LH. However, coinjection of these doses of beta-endorphin and alpha MSH suppressed plasma LH levels significantly within 15 min. beta-Endorphin (150 ng) produced a significant suppression of plasma LH levels. Furthermore, coadministration of 100 ng alpha MSH with 150 ng beta-endorphin lowered plasma LH for a longer period of time than this dose of beta-endorphin alone. Low doses of beta-endorphin (20 ng) or alpha MSH (100 ng) alone or in combination did not alter plasma GH levels. A higher dose of 150 ng beta-endorphin produced a slight elevation of plasma GH. This effect was potentiated 5-fold when 150 ng beta-endorphin were injected in combination with 100 ng alpha MSH. These results indicate that alpha MSH acts as an antagonist to beta-endorphin in regard to the secretion of PRL, whereas it potentiates the effect of beta-endorphin in stimulation of GH and inhibition of LH secretion.

Animals↗
PubMed1986

Gamma amino butyric acid (GABA) controls anterior pituitary hormone secretion.

Intraventricular injection (3V) of GABA can lead to a dose-related increase in plasma LH in ovariectomized (OVX) and OVX, estrogen-primed animals. Since the effects were blocked by the GABA receptor antagonist, bicucculine (B), they appear to be specific. These alterations in plasma LH were accompanied by alterations in hypothalamic LHRH, dopamine (DA) and norepinephrine (NE) content which suggests roles for all three compounds in the genesis of the increase in plasma LH. Since the DA receptor blocker pimozide (P) failed to block the elevation in LH induced by GABA it appears that the effect of GABA on LH release is mediated by NE. Others have found that the GABA agonist, muscimol, can lower plasma LH under certain conditions. Consequently, it appears likely that there may be opposite actions of GABA on LHRH release depending on the site of action within the hypothalamus. Intravenous (iv) injection of B in OVX rats produced an initial fall in plasma LH followed by a prolonged rise which again suggests several sites of action of GABA on LH release. GABA had no effect on FSH release consistent with separate control of this hormone. 3V injection of various doses of GABA produced a dose-related lowering of plasma TSH in OVX rats which appeared to be mediated by the dopaminergic system since P abolished the TSH-lowering of GABA. Following iv injection of B in normal male rats, there was a dramatic decline in TSH suggesting that under these conditions GABA would have a stimulatory action. Similar results were seen in OVX rats. The results indicate an important stimulatory action of GABA on TSH release in both males and OVX females. Perhaps the discrepancy between the results with B and GABA can be explained again by multiple sites of action of GABA of opposite sign. 3V injection of GABA induced a dose-related stimulation of growth hormone (GH) secretion; however, more recent evidence from other laboratories suggests that under certain conditions GABA has an inhibitory role in GH secretion. Again, we speculate that GABA had dual sites of action of opposite sign to affect GH. In contrast to the effects of GABA on these pituitary hormones, it appears to have a direct inhibitory effect on prolactin (Prl) secretion via the lactotrophs. Both stimulatory and inhibitory actions of GABA have been found following its injection into the brain. Studies with iv B also support dual actions on Prl release.

Adrenocorticotropic Hormone↗
PubMed1985

The influence of hGRF, CRF, TRH and LHRH on SRIF release from median eminence fragments.

The influence of 4 releasing factors on the release of somatostatin (SRIF) from the median eminence of the hypothalamus in rats was studied using an in vitro system. Synthetic growth hormone-releasing factor (hGRF-40) and corticotropin releasing factor (CRF) stimulated SRIF release, whereas thyrotrophin-releasing hormone (TRH) and luteinizing hormone releasing hormone (LHRH) did not stimulate its release. CRF and GRF may be physiologically involved in the regulation of SRIF release.

Animals↗
PubMed1985

Regulation of anterior pituitary and brain beta-adrenergic receptors by ovarian steroids.

Ovariectomy of adult female rats (200-230g) resulted in an increase in beta-adrenergic receptors in the cerebral cortex, hypothalamus and anterior pituitary. The anterior pituitary had the largest overall increase as well as the most rapid increase in beta-adrenergic receptor density of the tissues examined. The increase in hypothalamic or cerebral cortical beta-adrenergic receptors became apparent only long after ovariectomy (7-14 days). Fourteen days after ovariectomy, the density of beta-adrenergic receptors was 79%, 40%, and 24% in excess of control values in crude membranes prepared from anterior pituitary, hypothalamus and cerebral cortex, respectively. Over the same interval, the plasma concentration of luteinizing hormone (LH) increased 28-fold, while the concentration of follicle-stimulating hormone (FSH) rose 5-fold compared to control levels. Estradiol replacement (20 micrograms/kg/day) in these animals for four days before sacrifice concomitantly reduced plasma levels of the gonadotropins as well as the density of beta-adrenergic receptors in both the anterior pituitary and the hypothalamus. Long-term steroid replacement during the fifth and sixth week after ovariectomy, with implants of estradiol and progesterone which released the steroids in approximately physiological concentrations, significantly reduced beta-adrenergic density in anterior pituitary, but not in the hypothalamic membranes. This treatment significantly reduced plasma LH, but not FSH. Beta-adrenergic receptor density was also found to fluctuate significantly during the 4-day estrous cycle. The highest values were found on proestrus, and the lowest on diestrus 1. These studies indicate that changes in plasma concentrations of gonadal steroids (e.g. during the estrous cycle) influence the density of beta-adrenergic receptors in tissues involved in the control and release of anterior pituitary gonadotropins.

Animals↗
PubMed1985

Role of arginine vasopressin in control of ACTH and LH release during stress.

To determine the role of arginine vasopressin (AVP) in stress-induced release of anterior pituitary hormones, AVP antiserum or normal rabbit serum (NRS) was micro-injected into the 3rd ventricle of freely-moving, ovariectomized (OVX) female rats. A single 3 microliter injection was given, and 24 hours later, the injection was repeated 30 min prior to application of ether stress for 1 min. Although AVP antiserum had no effect on basal plasma ACTH concentrations, the elevation of plasma ACTH induced by ether stress was lowered significantly. Plasma LH tended to increase following ether stress but not significantly so; however, plasma LH following stress was significantly lower in the AVP antiserum-treated group than in the group pre-treated with NRS. Ether stress lowered plasma growth hormone (GH) levels and this lowering was slightly but significantly antagonized by AVP antiserum. Ether stress also elevated plasma prolactin (Prl) levels but these changes were not significantly modified by the antiserum. To evaluate any direct action of AVP on pituitary hormone secretion, the peptide was incubated with dispersed anterior pituitary cells for 2 hours. A dose-related release of ACTH occurred in doses ranging from 10 ng (10 p mole)-10 micrograms/tube, but there was no effect of AVP on release of LH. The release of other anterior pituitary hormones was also not affected except for a significant stimulation of TSH release at a high dose of AVP. The results indicate that AVP is involved in induction of ACTH and LH release during stress. The inhibitory action of the AVP antiserum on ACTH release may be mediated intrahypothalamically by blocking the stimulatory action of AVP on corticotropin-releasing factor (CRF) neurons and/or also in part by direct blockade of the stimulatory action of vasopressin on the pituitary. The effects of vasopressin on LH release are presumably brought about by blockade of a stimulatory action of AVP on the LHRH neuronal terminals.

Adrenocorticotropic Hormone↗
PubMed1985

Blockade of adrenal compensatory hypertrophy by unilateral hypothalamic lesions.

To determine if unilateral hypothalamic lesions block adrenal compensatory hypertrophy (ACH), such lesions were produced unilaterally under stereotaxic guidance using direct cathodal current in rats just after the left adrenal gland was removed. The animals were sacrificed one week later and the degree of the ACH of the remaining adrenal gland was determined. Animals without lesions uniformly showed ACH in terms of an absolute increase in adrenal weight of the remaining gland as compared to the one excised or if calculated as mg adrenal weight/100 g body weight. On the other hand, lesions in the region lateral to the paraventricular nucleus, lateral to the median eminence or in the region between these two loci prevented ACH in roughly 50% of the animals whether the lesion was placed on the same or opposite side of the hypothalamus. Some lesions in the mid-line in the vicinity of the paraventricular nucleus also resulted in blockade of ACH. We speculate that the blockade is due to a partial elimination of CRF and/or vasopressin/oxytocinergic pathways which are activated by the fall in plasma corticosterone after removal of an adrenal gland.

Adaptation, Physiological↗
PubMed1985

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

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 ultrashort-loop 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 min later, plasma ACTH was significantly higher 2 or 5 min after ether stress when compared with plasma ACTH in ether-stressed 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 ultrashort-loop feedback action to enhance stress-induced ACTH release and that this enhancement is not due to increased sensitivity of anterior pituitary corticotrophs to CRF.

Adrenocorticotropic Hormone↗
PubMed1985

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

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. Injections 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 micrograms (4.7-1175 pmol) of NPY. These inhibitory effects on LH release were dose dependent and lasted for at least 120 min after injection of 5.0 micrograms of NPY. Intraventricular injection of NPY also significantly decreased plasma growth hormone; however, the threshold dose was 2.0 micrograms (470 pmol), a dose 100-fold greater than the lowest dose that inhibited LH release. Plasma follicle-stimulating hormone was unaffected by injection of NPY. NPY (10(-6) and 10(-7) M) stimulated secretion of LH, growth hormone, and follicle-stimulating hormone from perifused anterior pituitary cells loaded in a Bio-Gel P-2 column. These results indicate that NPY acts on structures adjacent to the third ventricle to inhibit the secretion of LH and growth hormone but not follicle-stimulating hormone, whereas it can directly stimulate the secretion of all three hormones from the cells of the anterior pituitary in vitro. Since NPY has been found in the hypothalamus and median eminence, it is quite likely that it plays a physiologically significant role at both hypothalamic and pituitary sites: influencing secretion of pituitary hormones.

Animals↗