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Biomedical subjects

S M McCann

Publications and source records attributed to S M McCann.

At least 235 records · Page 13Linked to original sources
PubMed1985

Effects of intravenous and intraventricular injection of antisera directed against corticotropin-releasing factor on the secretion of anterior pituitary hormones.

To determine the physiological significance of corticotropin-releasing factor (CRF) in the control of pituitary hormone secretion, highly specific antibodies directed against the peptide were injected either intravenously or intraventricularly (third ventricle) and the effect on plasma levels of pituitary hormones was determined before and after application of ether stress for 1 min. The intravenous injection of CRF antiserum (0.5 ml) did not significantly alter basal corticotropin (ACTH) levels in freely moving ovariectomized rats but largely blocked the increase in plasma ACTH resulting from ether stress. These antibodies had no effect on the ether-induced decline in plasma growth hormone (GH), and they failed to modify plasma luteinizing hormone levels. In a second experiment, CRF antiserum (3 microliter) or normal rabbit serum was injected into the third ventricle. A blood sample was drawn 24 hr later and immediately thereafter another injection of CRF antiserum or normal rabbit serum was made. There was no modification in the level of any of the hormones 24 hr after the first injections, and they were similar in CRF antiserum and normal rabbit serum-injected animals. After imposition of ether stress, the response of plasma ACTH was nearly completely blocked by the intraventricular CRF antiserum, but the degree of blockade was slightly less than that obtained by intravenous injection. The decline in plasma GH after ether stress was blocked by the intraventricular CRF antiserum. There was no effect of the intraventricular injection of the antiserum on the levels of the other pituitary hormones. The results with intravenous injection of the antisera indicate that CRF plays an extremely important but probably not completely indispensable role in the release of ACTH after ether stress. The results of the intraventricular injection of the antiserum suggest strongly that endogenous CRF may also modify its own release in response to stress, augmenting it by a positive ultrashort loop feedback, and that the antisera against the peptide blocked this action; however, an action at the pituitary of these intraventricularly injected antibodies cannot be completely ruled out. The blockade of the stress-induced suppression of GH release by the CRF antibodies suggests that CRF released intrahypothalamically during ether stress brings about an alteration in the hypothalamic control of GH secretion such that the stress-induced inhibition of GH release is blocked.

Adrenocorticotropic Hormone↗
PubMed1985

Atrial natriuretic factor inhibits dehydration- and angiotensin II-induced water intake in the conscious, unrestrained rat.

Peptides isolated from atrial extracts possess potent natriuretic and diuretic activities. In general, these peptides, called atrial natriuretic factors (ANFs), oppose the actions of the water-conservatory peptides angiotensin II and vasopressin and are released from the heart in response to atrial stretch as a consequence of increased venous return. The recent description of ANF-like immunoreactivity in brain regions associated with the control of water intake suggested a role for these peptides in the neurogenic mechanisms of thirst. Intracerebroventricular (third ventricle) infusion of 1.0 or 2.0 nmol of ANF in conscious, overnight-dehydrated rats significantly inhibited subsequent water intake over a 2-hr test period. Intravenous infusion of 2.0 nmol, but not 1.0 nmol, of ANF resulted in a similar inhibitory action, suggesting that ANF released from the heart might act centrally to inhibit water intake by an action at one or more of the circumventricular organs. Water intake induced by central infusion of angiotensin II (9.6 and 25 pmol) in normally hydrated rats was significantly inhibited by prior infusion of 2.0 nmol of ANF. Water intake induced by higher doses of angiotensin II was not altered significantly by prior infusion of ANF. These results indicate a possible physiologic role for ANF in the hypothalamic control of water intake and reveal that the cardiac peptides can act centrally, as well as peripherally, to assist in the normalization of extracellular fluid volume.

Angiotensin II↗
PubMed1985

Short-term effects of vasoligation upon plasma follicle-stimulating hormone, luteinizing hormone, and prolactin in the adult rat: further evidence for a direct neural connection between the testes and the central nervous system.

The purpose of these experiments was to determine whether bilateral vasoligation of adult male rats had any short-term effects upon plasma levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin. Adult male rats (250-300 g) were either bilaterally vasoligated or sham vasoligated, and blood samples were obtained by cardiac puncture preoperatively and at 24 h and 7 days following surgery. Plasma levels of both FSH and LH were significantly (P less than 0.01) decreased at 24 h following vasoligation compared to preoperative levels and those of sham-operated controls. However, the response was differential since, at 7 days following vasoligation, plasma FSH was still significantly decreased while LH was returning to control levels. Conversely, plasma prolactin levels were significantly (P less than 0.01) increased at 24 h compared to preoperative values and those in sham-operated controls, and at 7 days prolactin had returned to preoperative control levels. Sham vasoligation did not significantly change plasma levels of FSH, LH, or prolactin at any of the time intervals investigated. These results provide further evidence that suggests that there may be a direct connection between the testis and central nervous system that may be involved in the short-term regulation of gonadotropin and prolactin secretion.

Animals↗
PubMed1985

Stimulation of somatostatin release from median eminence tissue incubated in vitro by taurine and related amino acids.

To determine if the putative amino acid transmitter taurine could affect the release of somatostatin (SRIF) from median eminence fragments, median eminences were incubated in vitro in the presence of various concentrations of taurine and its precursors, hypotaurine, cysteamine, cysteic acid, and L-cysteine sulfinic acid. Taurine was effective in releasing SRIF at doses of 50 microM and higher. Surprisingly, cysteic acid was the most potent stimulant of SRIF release, with a minimal effective dose of 0.1 microM. Cysteamine was effective at a dose of 50 microM, hypotaurine was effective only at 200 microM, and cysteine sulfinic acid was ineffective in stimulating SRIF release at any of the doses tested. To determine if the effect of taurine was mediated by the dopaminergic system, the dopamine receptor blocker pimozide (1 microM) was added to the medium containing either taurine or cysteic acid. Pimozide did not prevent the stimulatory effect of the amino acids. In conclusion, these investigations suggest that taurine and related amino acids may be involved in SRIF release by a nondopaminergic pathway. In view of the high concentrations of taurine in the hypothalamus it must be considered a putative transmitter releasing SRIF.

Amino Acids↗
PubMed1985

Effects of intraventricular growth hormone-releasing factor on growth hormone release: further evidence for ultrashort loop feedback.

We examined the effects of cerebroventricular injection of synthetic human GH-releasing factor [hGRF-(1-44)] on regulation of GH release in conscious male rats. These results were compared with the direct effects of hGRF on hormone released from dispersed anterior pituitary cells. Administration of two higher doses of hGRF (200 and 2000 ng) into the third ventricle (3V) produced a dose-related increase in plasma GH levels (P less than 0.001). Injection of hGRF into the 3V at two lower doses actually reduced GH release. Infusion of 20 ng (5 pmol) hGRF reduced plasma GH from 5-60 min (P less than 0.005), with a maximum suppression of 66%. The 2-ng (0.5-pmol) dose decreased GH secretion by 45% (P less than 0.05). hGRF stimulated a significant and dose-dependent release of GH from dispersed pituitary cells at concentrations of 10(-10) and 10(-9) M (P less than 0.025). The specificity of GRF for GH control, whether stimulatory or inhibitory, was seen by the failure of GRF to modify PRL, TSH, or LH release. Our results indicate that injection of larger doses of GRF into the 3V produce GH release, but at lower doses, 3V GRF may exert an action centrally to inhibit GH release. We propose that hypothalamic GRF may decrease its own neurosecretion by negative ultrashort loop feedback.

Animals↗
PubMed1985

Stimulation of somatostatin release in vitro by synthetic human growth hormone-releasing factor by a nondopaminergic mechanism.

The effect of synthetic human GH-releasing factor (hGRF-40) on somatostatin (SRIF) release from the median eminence of the hypothalamus was evaluated in rats with use of an in vitro incubation system. hGRF-40 stimulated SRIF release in a dose-related manner. This effect was significant at concentrations varying from 10(-11)-10(-7) M, with a minimal effective dose of 10(-11) M. Maximal stimulation was observed at 10(-10) M. Pimozide was added in vitro at a concentration of 10(-6) M to block dopamine (DA) receptors, since DA is a known stimulator of SRIF release. Pimozide was without effect on SRIF release and did not alter the stimulatory effect of hGRF-40. To evaluate the possibility that DA and GRF may share a common pathway to stimulate SRIF release, median eminence fragments were simultaneously exposed to submaximal concentrations of both DA (6 X 10(-7) M) and hGRF-40 (10(-12) M). By themselves, each of these doses had little effect on SRIF release. When they were added together, a marked stimulation was noted, which was not, however, significantly greater than the sum of the responses to each agent alone. These results suggest that DA and GRF act by separate mechanisms to stimulate SRIF release. GRF may be physiologically involved in the regulation of SRIF release. Stimulation of SRIF release may be a mechanism by which GRF exerts a negative ultrashort-loop feedback to inhibit GH release.

Animals↗
PubMed1985

The effect of gastrin-releasing peptide on growth hormone secretion in the rat.

Several investigators have reported gastrin-releasing peptide (GRP)-like immunostaining in several regions of the rat brain. The objective of this study was to determine the possible effects of this peptide on GH release. Porcine GRP was injected intraventricularly (third ventricular) in a volume of 2 microliters into ovariectomized female rats. A significant decrease in basal GH release, as evidenced by decreased plasma GH levels, was observed within 10 min which lasted for 90 min after the injection of 2 micrograms (0.7 nmol) GRP (P less than 0.001). In addition, all GH pulses were abolished during this time. In subsequent experiments, varying doses of GRP were administered, and human pancreatic GH-releasing factor (GRF) was injected iv at a dose of 0.1 microgram/kg 20 min later to determine the responsiveness of the pituitary. The minimal effective dose of GRP to lower plasma GH was approximately 10 ng (3.6 pmol); however, the GH-releasing action of GRF was blocked by even the lowest dose of the peptide tested (5 ng; 1.8 pmol). To determine if GRP had any direct action on the pituitary, overnight-cultured pituitary cells from ovariectomized animals were incubated for 1 h with GRP in various concentrations. There was a slight dose-dependent stimulation of GH release with concentrations of GRP ranging from 10(-9)-10(-6) M; however, the GH-releasing action was much less than that of GRF. To confirm the direct stimulatory effect of GRP on GH release, dispersed pituitary cells were perifused with medium containing 2 X 10(-6) M GRP. An immediate increase in GH release was observed in the perfusate. Since GRP has a direct stimulatory action to release GH in the pituitary, but ivt injection of the peptide inhibits GH release and blocks the response to GRF, we suggest that GRP may act on periventricular structures to release somatostatin, which reduces GH release and blocks the response to GRF.

Amino Acid Sequence↗
PubMed1985

Age-, sex-, and gonadal steroid-related changes in immunoreactive substance P in the rat anterior pituitary gland.

The interrelationship of anterior pituitary lobe (AP) immunoreactive substance P (I-SP) concentrations with age, sex, gonadal steroids, and estrous cyclicity in rats was examined. There was no difference between male and female AP I-SP levels at 0.5 month of age. At 2.0 and 5.0 months of age, a sex-linked difference in AP I-SP concentrations was evident, inasmuch as male APs contained approximately 3 and 8 times greater concentrations of I-SP, respectively, than APs from age-matched females. Long term (6 weeks) gonadectomy of adult rats resulted in an increase in I-SP concentrations in female APs and a decrease in the concentrations of the peptide in male APs compared to values in their respective sham-operated controls. Treatment of gonadectomized animals for the same length of time with gonadal steroid-filled Silastic capsule implants resulted in qualitatively identical responses in males and females; that is, estradiol benzoate decreased and 5 alpha-dihydrotestosterone propionate increased AP I-SP levels compared to the respective control values in castrates. Testosterone propionate treatment had no effect on AP I-SP levels compared with the respective gonadectomy control values. Short term (8 days) gonadectomy of adult males did not affect the AP concentration of I-SP. Likewise, gonadectomy of adult females was ineffective in altering the AP I-SP concentration compared with concentrations in females on diestrous day 1, diestrous day 2, proestrous, or estrous stages of the vaginal cycle. These data suggest that gonadal steroids are physiologically important in the regulation of I-SP concentrations in the AP. We hypothesize that I-SP is indigenous to the AP and that gonadal steroids act directly at the level of the AP to affect the synthesis and/or release of the peptide.

Age Factors↗
PubMed1985

On the mechanism of growth hormone autofeedback regulation: possible role of somatostatin and growth hormone-releasing factor.

To determine the role of somatostatin (SRIF) and GH-releasing factor (GRF) in GH autofeedback, 20 micrograms rat GH in 2 microliter were injected into the third ventricle (IVT) 1 or 3 h before injection of the alpha 2-receptor stimulator clonidine (50 micrograms/kg, iv), which elevates plasma GH and TSH levels in normal rats. GH preinjected 1 or 3 h before clonidine significantly suppressed the clonidine-induced GH surge, whereas TSH release was not affected by GH. Preinjection of ovine LH IVT following the same protocol did not inhibit the clonidine-induced GH surge, suggesting a specific effect of IVT GH. Passive immunization with 400 microliters sheep antisomatostatin serum did not reverse the inhibition of the clonidine-induced GH surge by exogenous GH administered IVT either 1 or 3 h before clonidine. The TSH response was augmented by this procedure. Furthermore, IVT GH did not reduce the surges of GH and TSH elicited by GRF (250 ng/kg, iv) and TRH (150 ng/kg, iv) administered 1 or 3 h after IVT rat GH. These results suggest that GH autofeedback is mediated by reduced GRF secretion, rather than enhanced SRIF release.

Animals↗
PubMed1985

Stress-induced secretion of alpha-melanocyte-stimulating hormone and its physiological role in modulating the secretion of prolactin and luteinizing hormone in the female rat.

The pattern of alpha MSH release during immobilization stress in ovariectomized rats was determined and correlated with that of plasma PRL and LH. Stress induced a marked elevation in plasma immunoreactive alpha MSH, with a time course identical to that of plasma PRL. The increment in plasma PRL was greater than that in plasma alpha MSH. Plasma LH was markedly lowered by stress. Analysis of pituitary and hypothalamic alpha MSH indicated a significant (P less than 0.05) increase in the neurointermediate lobe and anterior lobe content of alpha MSH. The alpha MSH content in the hypothalamus was lowered by stress when expressed as tissue content (P less than 0.025), although no significant differences in content in this area were detected when the results were expressed in terms of tissue protein. Stress induced a marked increase (P less than 0.01) in the median eminence levels of alpha MSH. Intraventricular (third ventricle) injection of the gamma-globulin fraction of a specific antiserum raised against alpha MSH increased basal PRL levels (P less than 0.025) and prevented the decline in plasma PRL that occurred 60 min after the onset of stress in the normal rabbit serum-injected rats. The stress-induced suppression of plasma LH was attenuated and delayed by the administration of alpha MSH antibodies. In conclusion, alpha MSH of brain origin is released during stress and is involved in lowering plasma PRL to basal levels and producing a partial suppression of plasma LH.

Animals↗
PubMed1985

Purification of a non-dopaminergic and non-GABAergic prolactin release-inhibiting factor (PIF) in sheep stalk-median eminence.

Prolactin release-inhibiting factor (PIF) extracted from 1200 sheep stalk-median eminences was purified by gel filtration on a Sephadex G-25 column (4.5 X 150 cm). PIF activity was determined by measuring the inhibition of prolactin release from dispersed anterior pituitary cells of adult male or estrogen-primed, ovariectomized rats. Using this system, PIF was detected in tube fractions 122-127 (volume = 20 ml/tube). These fractions also contained LHRH and somatostatin; however, these peptides had no prolactin-inhibiting activity in the quantities present. No dopamine or gamma-aminobutyric acid (GABA) was detected in the active fractions by radioenzymatic assay and fluorophotoenzymatic assay, respectively. Furthermore, receptor blockers for dopamine or GABA did not interfere with the PIF activity. These findings indicate that the PIF activity cannot be attributed to either dopamine or GABA, both of which are known to inhibit prolactin release, and provide evidence for the presence of a non-dopaminergic and non-GABAergic PIF within the hypothalamus.

Animals↗
PubMed1985

Possible negative ultra-short loop feedback of luteinizing hormone releasing hormone (LHRH) in the ovariectomized rat.

To determine if LHRH might act within the brain to modify its own release, repeated blood samples were removed from conscious ovariectomized rats and minute doses of LHRH were injected into the third ventricle (3V). The effect of these injections on plasma LH and FSH was measured by radioimmunoassay (RIA). The higher dose of intraventricular LHRH (10 ng in 2 microliter) induced an increase in plasma LH within 10 min after its injection. Plasma LH decreased for the next 60 min. This was followed by restoration of LH pulses characteristic of the ovariectomized rat. This dose of LHRH slightly elevated plasma FSH concentrations. In stark contrast, a 10 fold lower dose of 1 ng of LHRH injected into the ventricle resulted in a highly significant decrease of plasma LH at 10 min following injection, followed by return of LH pulsations. There was no effect on the pulsatile release of FSH. The results are interpreted to mean that at the higher dose, sufficient LHRH reached the site of origin of the hypophyseal portal vessels in the median eminence so that it diffused into portal vessels and was delivered to the gonadotrophs to induce LH release. In contrast, the lower dose provided sufficient hypothalamic concentrations of the peptide to suppress the discharge of the LHRH neurons, thereby leading to a decline in plasma LH, indicative of an ultrashort-loop negative feedback of LHRH to suppress its own release.

Animals↗
PubMed1984

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

The effects of intravenous or intraventricular injection of synthetic ovine corticotrophin-releasing factor (oCRF) on plasma levels of anterior pituitary hormones were studied in conscious, ovariectomized (OVX) female rats and compared with the actions of the peptide on dispersed anterior pituitary cells from OVX female rats incubated in the presence of CRF. Third ventricular injection of oCRF in freely moving rats caused a significant increase in plasma levels of ACTH in a dose-related manner with a minimal effective dose of less than 0.5 micrograms (0.1 nmol). The effect was observable at 5 min after injection and persisted for the 60 min duration of the experiment. In contrast, growth hormone levels were significantly depressed within 15 min with a minimal effective intraventricular dose of 0.5 micrograms. The suppression persisted for the duration of the experiment but there was no additional effect of the higher dose of 5 micrograms. Plasma LH levels were also lowered by the highest dose of 5 micrograms (1.0 nmol) of oCRF, with the first significant lowering at 30 min. Lower doses had no effect on plasma LH. Plasma TSH levels were not significantly altered. Control injections of the 0.9% NaCl diluent were without effect on the levels of any of the hormones. Intravenous injection of similar doses of oCRF had no effect on plasma levels of GH or LH. The ACTH-releasing action of the oCRF preparation was confirmed by in vitro incubation of the peptide with dispersed anterior pituitary cells for 2 h. A dose-related release of ACTH occurred in doses ranging from 0.1-10 nM, but there were no effects on the release of the other anterior pituitary hormones. The results suggest that oCRF may act within the hypothalamus to suppress the release of GH and to a lesser extent LH. The stimulation of ACTH release following intraventricular CRF is presumably related to its uptake by portal blood vessels with delivery to the pituitary and stimulation of the corticotrophs.

Adrenocorticotropic Hormone↗
PubMed1984

Testosterone control of brain and anterior pituitary beta-adrenergic receptors.

Orchidectomy of adult albino rats resulted in a quick, (approximately 70%) increase in the density of beta-adrenergic receptors in the anterior pituitary gland within the first day. There was a concurrent rapid increase in plasma levels of pituitary gonadotropins. The beta-receptor density continued to increase slowly for at least 16 days after castration, but it could be lowered significantly to the levels of sham-operated animals by treatment with testosterone (3 mg/kg/day) beginning on the fourth day after castration and continuing for 4 days. This treatment also completely reversed the elevation in plasma levels of luteinizing hormone (LH), and significantly reduced the circulating follicle-stimulating hormone (FSH) levels. Prolactin levels were not significantly altered by the treatments used in these studies. Most of the beta-adrenergic receptors induced by orchidectomy in the anterior pituitary were shown, using a beta 1-selective antagonist, practolol, or a beta 2-selective antagonist, IPS-339, to be of the beta 2-subtype. The density of the beta-adrenergic receptors in the cerebral cortex also increased significantly (10-24%) after castration, and returned to the levels of sham-operated animals following treatment with testosterone. No significant change in the density of the beta-adrenergic receptors in the hypothalamus resulted from either castration or testosterone replacement.

Animals↗
PubMed1984

Differential role of the opioid mu and delta receptors in the activation of prolactin (PRL) and growth hormone (GH) secretion by morphine in the male rat.

Administration of naloxazone (50 mg/kg i.v.), an irreversible, selective and long acting antagonist of the mu 1 subclass of the opioid receptors, strongly reduced stimulation of PRL secretion by morphine (5.0 mg/kg i.v.) injected 24 hours later into conscious, unrestrained rats. In contrast, the effect of morphine on PRL release was unimpaired in rats treated 24 hours beforehand with either the reversible opioid antagonist naloxone (50 mg/kg i.v.), or the vehicle for naloxazone. A complete suppression of the PRL response to morphine (3.0 mg/kg i.v.) was observed in animals given intraventricular (IVT) injection of beta- funaltrexamine (beta-FNA, 2.5 micrograms), another selective, irreversible and long acting antagonist of the mu receptors, 24 hours beforehand. Neither naloxazone nor beta-FNA had any effect on the activation of GH secretion by morphine, which, however, was conspicuously reduced by ICI 154, 129, a preferential delta receptor antagonist, injected IVT (50 micrograms) 5 minutes before morphine. ICI 154, 129 had no effect on the PRL response to morphine. It is concluded that the PRL stimulating effect of morphine is mediated by the mu receptors, whereas activation of GH probably involves the delta sites.

Animals↗
PubMed1984

Partial characterization of immunoreactive substance P in the rat pituitary gland.

Two distinct carboxy-terminus-directed anti-substance P (SP) sera (R-1C and R-6G) were used to characterize immunoreactive SP (I-SP) in acetic acid extracts of anterior pituitary (AP) and posterior pituitary (PP) glands of adult male rats. The tissue concentrations of I-SP measured by R-1C and R-6G were comparable. The contents of I-SP were 600-1150 pg/AP and 25-52 pg/PP. I-luteinizing hormone releasing hormone and I-somatostatin (I-SOM) were undetectable in AP extracts, but PP extracts contained the equivalents of 325-785 pg I-SOM/gland. Serial dilutions of AP and PP extracts produced displacement curves with both SP antisera that were parallel to the respective synthetic SP standard and hypothalamic extract displacement curves. Gel filtrations of AP and PP extracts on a Sephadex G-25 column produced I-SP peaks eluting in the same fractions as synthetic SP and hypothalamic I-SP. However, the AP I-SP profile also revealed a side peak migrating between the void volume and the major I-SP peak. Neither immunoreactive species in the AP extract were eliminated when eluted with 6.0 M guanidine HCl, a strong denaturing agent. In vitro incubation of paired anterior hemipituitaries for 30 min in the presence of a 56 mM K+ concentration resulted in a significant (p less than .0001), 25-fold increase in the release of I-SP into the incubation medium above the mean control value. Radiofrequency lesions placed in the median eminence-arcuate region of male rats caused a significant (p less than .001) reduction of I-SP in both the AP and PP. These reductions were inversely related to the plasma prolactin values. The elevation in plasma prolactin was taken as an index of completeness of lesions. We conclude that: 1) the rat pituitary contains I-SP as assessed by its immunologic and chromatographic behavior, 2) K+ depolarization is a potent stimulator of the release of AP I-SP in vitro, 3) the ME-arcuate region is important for the maintenance of pituitary I-SP levels in the rat.

Amino Acid Sequence↗
PubMed1984

Presence and possible site of action of secretin in the rat pituitary and hypothalamus.

Secretin-like immunoreactivity was detected in extracts of several rat brain structures by radioimmunoassay, most notably in the pituitary, hypothalamus, pineal and septum. Its localization to these structures suggested that it might play a role in neuroendocrine events similar to its structural homolog vasoactive intestinal peptide. Dose-related stimulations (MED, 10(-7) M) of prolactin (PRL) release were observed after incubation of synthetic secretin with dispersed, cultured pituitary cells from male and ovariectomized (OVX) female rats. In OVX females, i.v. infusion of a high dose of secretin (10 micrograms) resulted in a significant elevation of PRL levels. Doses of secretin as low as 0.1 micrograms when administered into the third cerebroventricle were capable of significantly inhibiting PRL release in both males and OVX females, suggesting an ultrashort-loop, negative feedback of secretin. Secretin can now be added to the growing list of putative PRL-releasing agents.

Animals↗