Biomedical subjects

S M McCann

Publications and source records attributed to S M McCann.

At least 163 records · Page 9Linked to original sources

PubMed1990

The role of LH in the autofeedback inhibition of LH and FSH secretion in ovariectomized rats.

This study examined the role of exogenous LH in the autofeedback regulation of LH and FSH release in ovariectomized rats. The rats were implanted with third ventricular cannulae three weeks after ovariectomy and fitted with silastic jugular cannulae one week later. Baseline hormone levels were established on the day of experimentation in conscious, unrestrained animals. Thereafter, experimental animals received intraventricularly (IVT) either a 9 ug or 20 ug dose of a purified preparation of human (h)LH that did not crossreact in our rLH RIA. In response to 20 ug, but not 9 ug of LH, plasma levels of both LH and FSH were significantly reduced during the following one hour period compared to values in controls receiving buffer IVT. Administration of ovine (o)LH (6 ug, IVT), a preparation which crossreacts in the rLH RIA, significantly elevated plasma levels of detectable LH during the experimental period indicating that LH reaches the blood stream from the third ventricle and, thus, may effect endogenous hormone release at either the pituitary or hypothalamic levels. However, in animals preinjected with 9 or 20 ug of hLH IVT one hour earlier the surge of both LH and FSH in response to LHRH (25 ng iv) was not different from that in the buffer-injected controls receiving LHRH which indicates that pituitary responsiveness was not suppressed by the effective dose of hLH. The results of this study suggest that the inhibitory shortloop feedback of LH on endogenous LH and FSH secretion in ovariectomized rats occurs at the level of the hypothalamus.

Animals↗

PubMed1990

Stimulatory role of substance P on gonadotropin release in ovariectomized rats.

Substance P (SP) has been shown to be present in the hypothalamus and anterior pituitary. To evaluate a possible physiological role of endogenous SP in the control of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release, specific antiserum against SP (anti-SP) was injected intraventricularly (3 microliters into the third ventricle) or intravenously (50 or 200 microliters) into conscious, ovariectomized (OVX) rats. Third ventricular injection of the antiserum induced a significant decrease in both plasma LH and FSH levels when compared to values in control animals injected with normal rabbit serum (p less than 0.01 and p less than 0.025, respectively). The effect was observed within 10 mi and levels remained suppressed for 60 min. In contrast, intravenous injection of large doses of anti-SP had no effect on the release of both hormones. In order to confirm the stimulatory effect of SP itself, synthetic SP was injected intravenously and intraventricularly into estrogen-primed (E-primed), OVX rats. Synthetic SP dramatically stimulated LH release, but not FSH release when injected either intravenously or intraventricularly at doses of 10 and 50 micrograms (p less than 0.001, p less than 0.005 vs. control, respectively). To investigate any direct action of SP on gonadotropin release from the anterior pituitary gland, synthetic SP was incubated with dispersed anterior pituitary cells harvested from E-primed OVX rats. SP did not affect the release of gonadotropins in vitro. These results indicate that endogenous hypothalamic SP exerts a tonic stimulatory hypothalamic control of basal gonadotropin release in OVX rats.

Animals↗

PubMed1990

Opposite effects of central immunoneutralization of angiotensin II or atrial natriuretic peptide on luteinizing hormone release in ovariectomized rats.

Studies both in vivo and in vitro have provided evidence that LH secretion can be altered by angiotensin II (AII) or atrial natriuretic peptide (ANP); however, the physiological significance of these endogenous neuropeptides in the control of gonadotropin release is still unclear. We studied the effects of central immunoneutralization of these neuropeptides on LH and FSH release in ovariectomized rats. Antisera directed against AII or ANP were microinjected into the third cerebral ventricle (3V) of conscious, unrestrained rats with indwelling external jugular catheters and blood samples were withdrawn immediately prior to the injections and at various intervals thereafter. Plasma LH was not altered initially but by 2 h was significantly lower in the animals injected with antiserum directed against AII (AB-AII) than in controls injected with normal rabbit serum (NRS). Values remained low for 6 h. By 24 h they had returned to levels similar to those of NRS-injected controls. On the other hand, in animals injected with antiserum against ANP (AB-ANP) plasma LH levels were significantly higher than those of controls (NRS) after a delay of 4 h. Values were still significantly elevated at 24 h. There was no difference in plasma FSH concentrations between control groups (NRS) and groups injected with either AB-AII or AB-ANP. These results indicate that endogenous AII and ANP play no role in the control of FSH release, at least in ovariectomized rats but that these neuropeptides play a role in LH release which is stimulated by AII and inhibited by ANP since the immunoneutralization decreased and increased, respectively, the plasma levels of this hormone.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMed1990

The role of calcitonin gene-related peptide in the control of growth hormone and prolactin release.

In order to evaluate the actions of calcitonin gene-related peptide (CGRP), a neuropeptide which is found within the hypothalamus, male and ovariectomized (OVX) female rats were injected intraventricularly (third ventricle, 3V) with varying doses of CGRP or antiserum directed against the peptide and the effect on plasma growth hormone (GH) and prolactin (Prl) concentrations studied. Intraventricular injection of the peptide (0.5 or 5.0 micrograms; 0.125 or 1.25 nmol) induced a suppression of GH release in conscious, OVX female and intact male rats. Conversely, intraventricular injection of diluted (1:10) highly specific antiserum against the peptide produced the reverse effect and a transient elevation in plasma GH occurring 2 h after the injection in males. A longer-lasting elevation occurred in OVX females which persisted for the 24-hour duration of the experiment. The elevation was delayed as has been the case with other antisera suggesting that the site of action was at some distance from the site of injection into the 3V. Since the peptide had an action to inhibit GH release from dispersed, overnight cultured anterior pituitary cells in vitro at doses of 10(-11) M, it is not certain from these results whether or not the effects of the peptide are exerted directly on the hypothalamus or the pituitary, but the results indicate a physiologically significant action of this peptide to suppress GH release. Similarly, intraventricular injection of the peptide produced a dose-related suppression of Prl release in OVX animals; however, antiserum directed against the peptide failed to alter Prl release. In males, only the lower 0.5-microgram dose effectively inhibited Prl release.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Physiologically significant inhibitory hypothalamic action of substance P on prolactin release in the male rat.

To evaluate a possible physiological role of endogenous substance P (SP) in the control of prolactin (PRL) release, conscious adult male rats were given injections of a specific antiserum against SP (anti-SP) into the third ventricle (3 microliters) or intravenously (0.5 ml). Third-ventricular injection of anti-SP induced a significant increase in plasma PRL levels when compared to values in control animals injected with normal rabbit serum (p less than 0.02). Plasma PRL concentrations were significantly elevated within 2 h after injection of antiserum and remained elevated for the 4-hour duration of the experiment. In contrast, injections of large doses of anti-SP intravenously had no effect on plasma PRL levels. In order to confirm the effect of SP itself, synthetic SP was injected intravenously and intraventricularly. Opposite effects of SP on PRL release were observed after intravenous and intraventricular injections of low or high doses of the peptide. A lower dose of SP (10 ng, 7.42 pmol) injected into the third ventricle suppressed the release of PRL (p less than 0.01), whereas higher doses (1 microgram, 0.74 nmol, or 5 micrograms, 3.71 nmol) had a stimulatory effect on PRL release (p less than 0.01). Similarly, a low dose of SP (0.1 microgram, 0.07 nmol) injected intravenously lowered plasma PRL (p less than 0.05). Large doses of intravenous SP (50 micrograms, 37.1 nmol) dramatically stimulated PRL release (p less than 0.001). To evaluate a possible direct action of SP on PRL release from the anterior pituitary, the peptide was incubated with dispersed anterior pituitary cells for 1 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Role of arachidonic acid or its metabolites in growth-hormone-releasing factor-induced release of somatostatin from the median eminence.

The possible involvement of arachidonic acid (AA) release in growth-hormone-releasing factor (GRF)-induced somatostatin (SRIF) release from the median eminence (ME) of the hypothalamus was evaluated in adult male rats using an in vitro incubation system. The MEs were preincubated with [14C]-AA, then washed and incubated with vehicle or test agents, and the release of SRIF and [14C]-AA into the medium was measured. In the experiments designed only to determine SRIF release, the MEs were first preincubated for 30 min. The medium was then discarded and replaced with fresh buffer or test substances and incubated for 10, 20 and/or 30 min. GRF (10(-10) M) stimulated both AA and SRIF release significantly within 20 min, with maximum release occurring at 30 min. The stimulatory effect of GRF on AA release was coincident with the release of SRIF. A phospholipase A2 inhibitor (10(-6) M, quinacrine) completely abolished the stimulatory effect of GRF on both AA and SRIF release. The release of SRIF induced by GRF was also inhibited by both indomethacin (10(-6) M, a cyclooxygenase inhibitor) and metyrapone (10(-6) M, a cytochrome P-450 inhibitor). On the other hand, nordihydroguaiaretic acid (10(-6) M, a lipoxygenase inhibitor) had no effect on GRF-evoked SRIF release. The data presented here suggest that an important GRF-mediated event leading to SRIF secretion is an elevated release of AA from ME fragments in vitro. In conclusion, our data are suggestive that the stimulatory effect of GRF on SRIF release is due, in part, to the release and subsequent metabolism of AA to one or more metabolites.

Animals↗

PubMed1990

Physiological significance of the negative short-loop feedback of prolactin.

The aim of the present study was to evaluate the physiological significance of the rapid, short-loop, negative feedback of prolactin by passive immunization with antiserum to rat prolactin injected into the third cerebral ventricle (3V) of conscious, freely moving intact or castrated male rats. Blood samples for measurement of plasma prolactin concentrations were removed through implanted external jugular catheters. After injection of 3 microliters of undiluted antiserum, plasma levels of prolactin decreased rapidly (within 5 min) to values undetectable by RIA. Further study revealed that this dose of antiprolactin serum had combined with circulating prolactin, thus rendering it undetectable by RIA. To overcome this problem, we repeated the experiment injecting 2 microliters of diluted antiserum (dilution factors 20, 100, 200, 2,000) into the 3V. When compared to values of plasma prolactin in control rats injected with 2 microliters of normal rabbit serum, none of the dilutions of antiserum induced a significant change in prolactin concentrations for as long as 4 h after injection. Since there was no effect of intraventricularly injected antiprolactin serum on basal prolactin secretion, in the next experiment, intact as well as castrated male rats were subjected to ether stress 30 min after intraventricular injection of antiserum (dilution factor 100). The elevation of plasma prolactin which followed ether stress was significantly higher in male rats pretreated with antiprolactin serum than that which occurred in control rats. A similar enhancement of the increase in plasma prolactin following ether stress, but of longer duration, was obtained in castrated rats injected with antiprolactin serum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Physiologically significant effect of neuropeptide Y to suppress growth hormone release by stimulating somatostatin discharge.

Neuropeptide Y (NPY) is a peptide found in a variety of hypothalamic loci which is frequently colocalized with catecholamines. It is also secreted into hypophyseal portal vessels. The injection of NPY into the third ventricle (3V) lowered plasma GH levels in conscious, freely moving male rats. To determine the physiological significance of the hypothalamic inhibitory action of the peptide, highly specific antiserum directed against NPY was injected into the 3V of conscious rats. 3V injection of the antiserum evoked a significant elevation of plasma GH within 2 h on comparison to values in normal rabbit serum-injected, ovariectomized rats. The difference increased and reached a maximum at 6 h after injection. On the other hand, there was no effect of the antiserum in ovariectomized, estrogen, progesterone-blocked rats. Intraventricular injection of the anti-NPY serum also caused a significant elevation of plasma GH within 2 h in normal male rats and the increases above values in normal rat serum-injected control animals became even more significant at 3 and 4 h. To determine the mechanism by which NPY lowers GH after its intraventricular injection, its effect on the release of somatostatin (SRIF) from median eminence fragments incubated in vitro was examined. NPY stimulated SRIF release with a highly significant effect at a concentration of 10(-9) M. Borderline stimulation was observed at doses as low as 10(-11) M. The curve was bell-shaped with a declining release at 10(-8) M and 10(-7) M. The releasing action of NPY was blocked by either the alpha 1-receptor blocker, prazosin (10(-6) M), or the beta-receptor blocker, propranolol (10(-6) M), but was not affected by the alpha 2-receptor blocker, yohimbine (10(-6) M). We conclude that NPY has a physiologically significant inhibitory action within the hypothalamus to suppress GH release in ovariectomized female and intact male rats by stimulation of SRIF release by alpha 1 and beta-adrenergic receptor-mediated mechanisms.

Animals↗

PubMed1990

The role of neuropeptide Y (NPY) in control of gonadotropin and prolactin release in the rat.

Neuropeptide Y is a peptide found in a variety of hypothalamic loci which is frequently colocalized with catecholamines. It is also secreted into hypophyseal portal vessels. We have previously evaluated the effects of this peptide on FSH, LH and prolactin release. In ovariectomized females neuropeptide Y inhibits LH release. It has similarly been reported to inhibit LH release in intact males; however, estrogen priming of ovariectomized animals converts this inhibitory action into a stimulatory effect. In ovariectomized animals the peptide has a direct stimulatory effect on perifused pituitary cells, enhancing the release of both FSH and LH, an effect which is contrary to that obtained with LH release after intraventricular injection of the peptide. In the present experiments the physiological significance of these effects has been evaluated by the intraventricular injection (3V) of highly specific antiserum directed against the peptide. In ovariectomized and in ovariectomized, estrogen-primed rats, the third ventricular injection of antiserum had no effect on gonadotropin release. In male rats intraventricular injection of the antiserum elevated LH, which indicates that the inhibitory action of the peptide seen in intact males is of physiological significance. However, it has been reported by others that the proestrous type discharge of LH-RH is blocked by intraventricular injection of neuropeptide Y antiserum. Neuropeptide Y might therefore play an essential role in the preovulatory release of LH. On the other hand, others have shown that intraventricular injection of neuropeptide Y in male rats can either stimulate, at low doses, or inhibit, at high doses, the release of prolactin. We have confirmed the inhibitory action, which appears to be of physiological significance since antisera directed against the peptide injected intraventricularly resulted in an elevation of prolactin release. The results of these studies indicate that neuropeptide Y plays a very important and often physiologically significant role in the control of LH and prolactin release by hypothalamic action.

Animals↗

PubMed1990

Involvement of beta-adrenergic receptors in the differential release of gonadotropins in acutely orchidectomized rats.

To determine the differential release of gonadotropins in acutely orchidectomized rats, a single injection of the beta-adrenergic blocker Bornaprolol (FM 24) was administered to the animals and plasma FSH and LH levels were determined. FM 24 produced low plasma FSH levels only when injected 16 h before starting the blood collection and had no effect on FSH levels at 0, 30 and 46 h after its administration. However, it produced low LH plasma levels at 0, 16 and 30 h after administration. These findings confirm that pituitary beta-adrenergic receptors are involved in plasma LH release and suggest that they could also be involved in the differential release of FSH/LH.

Adrenergic beta-Antagonists↗

PubMed1990

Physiological role of neuropeptide Y (NPY) in control of anterior pituitary hormone release in the rat.

Neuropeptide Y (NPY) is a peptide originally isolated from porcine brain and subsequently shown to be widely distributed in the body of several species, including man. Neuropeptide Y is a circulating peptide; however, blood levels were higher in portal than peripheral blood of anesthesized rats. Earlier studies in ovariectomized and intact male rats have shown that intraventricular injection of NPY inhibits release of growth hormone (GH) and luteinizing hormone (LH) without producing significant modification of plasma follicle stimulating hormone (FSH) and thyrotropin stimulating hormone (TSH). In the male low doses of NPY elevate prolactin (PRL) whereas high doses suppress its release. To assess the physiologic significance of these actions, we injected a highly specific anti-NPY serum (aNPY) into the third cerebral ventricle (3V) of unrestrained male, ovariectomized, and ovariectomized, estrogen progesterone blocked rats and measured plasma GH, PRL, LH and TSH by blood sampling via indwelling jugular catheters. Third ventricular injection of aNPY (2 microliters of 1:10 dilution) caused a significant elevation of plasma GH levels after 3 and 4 h compared to the values in NRS (1:10)-injected rats. To determine if these changes were due to alterations in pituitary responsiveness to somatostatin, the rats were injected intravenously with a challenge dose of somatostatin (0.5 microgram) 2 h after previous injection of aNPY or NRS, and blood samples were taken every 10 min for 30 min. The responses did not differ in both groups which indicated that the antiserum was not acting directly on the pituitary gland.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Blockade of volume expansion-induced release of atrial natriuretic peptide by median eminence lesions in the rat.

Since stimulation of the anteroventral third ventricle region (AV3V) induced a rapid elevation of plasma atrial natriuretic peptide (ANP) associated with rapid changes in brain and pituitary content of ANP, whereas lesions of the AV3V were followed by a marked decline in plasma, brain and pituitary content of the peptide, we hypothesized that release of ANP from the median eminence (ME) might be an important pathway to control plasma ANP. Consequently, electrolytic lesions were placed in the ME and the response to hypertonic-volume expansion was determined in conscious rats. In sham-operated controls volume expansion produced a 3.5-fold increase in plasma ANP concentrations within 5 min. Values rapidly declined to near initial levels at 15 and 30 min. Median eminence lesions almost completely blocked the response to volume expansion at 24 and 120 h post-lesion and initial ANP concentrations were lower than those of the sham-operated controls. The results indicate that increased release of ANP from the neurohypophysis may play an important role in the increased plasma ANP concentrations which follow volume expansion.

Animals↗

PubMed1990

Angiotensin II antiserum decreases luteinizing hormone-releasing hormone in the median eminence and preoptic area of the rat.

Ovariectomized female rats were sacrificed 3 h after intracerebroventricular microinjection of normal rabbit serum (NRS), specific antiserum against angiotensin II (AB-AII) or atrial natriuretic factor (AB-ANF). AB-AII decreased plasma LH by 50% and LH-RH content by 70% in the median eminence and medial preoptic area, respectively, but did not change plasma FSH when compared to animals which received NRS. There was no difference in these parameters when the animals were injected with AB-ANF or NRS. These results indicate that endogenous AII plays a physiological role in LH release acting directly or indirectly through LH-RH neurons of the median eminence and medial preoptic area.

Angiotensin II↗

PubMed1989

Differential effects of naloxone on basal and stress-induced release of ACTH and prolactin in the male rat.

The effect of i.v. injection of various doses of naloxone (NAL) on plasma adrenocorticotropin (ACTH) and prolactin (Prl) in conscious animals bearing an indwelling intrajugular catheter was assessed. The effects were evaluated in animals which were left undisturbed and in others subjected to either restraint or ether stress. The results revealed that the dose of 3 mg/kg of NAL significantly reduced basal Prl levels, whereas a dose of 6 mg/kg of NAL was required to block completely either ether or restraint stress-induced release of Prl. The behavior of ACTH contrasted with that of Prl. There was no effect whatsoever of the 3 mg/kg dose of NAL on either resting or stress-induced ACTH levels, whereas a 6 mg/kg or 12 mg/kg dose of NAL elevated resting ACTH levels and only partially attenuated the further elevation induced by stress in these animals. The results clearly indicate a NAL sensitive step in the control of resting and stress-induced Prl release but indicate that the control of resting and stress-induced release of ACTH is different in that the predominantly millimicron receptor blocker, NAL, can elevate ACTH at high doses and can only partially block the response to stress. In contrast to Prl where opioid peptide control is solely stimulatory, this control of ACTH secretion appears to have both stimulatory and inhibitory features.

Adrenocorticotropic Hormone↗

PubMed1989

Methods for the study of somatostatin.

It is clear from the above that there are a number of methods for study of SRIF release. From the standpoint of convenience, the in vitro static incubation of ME is the most practical technique at the present time. Using this preparation SRIF release has been found to be modified by a number of neurotransmitters and peptides, and studies on the mechanism of release of the peptide have been initiated. There is no doubt that such studies should be complemented by perifusion studies, by studies involving larger pieces of the hypothalamus which encompass the entire somatostatinergic neuron, and by in vivo studies to determine the correlation of in vivo and in vitro release. Among the in vivo techniques which have been utilized, the push-pull cannula technique employing cannulae implanted in hypothalamus or anterior pituitary gland offers the most promise. A summary of the effects of some neurotransmitters and neuropeptides on hypothalamic SRIF secretion is reported in Table. I.

Animals↗

PubMed1989

Altered gonadotropin and prolactin release induced by median eminence (ME) lesions and pharmacological manipulation of prolactin release: further evidence for separate hypothalamic control of FSH and LH release.

To delineate more clearly the regions of the median eminence involved in the control of gonadotropin secretion, electrolytic lesions were made in the median eminence of adult male rats. Also the role of prolactin in the maintenance of gonadotropin secretion and sex organs was further evaluated by the administration of alpha-bromo-ergocryptine (CB154) or its diluent SC to lower prolactin via its dopamine agonist action in these animals with lesions. The effects of elevation of prolactin by the administration in the drinking water of the dopamine antagonist, sulpiride, were also evaluated in intact rats. At the conclusion of the experiments the localization of lesions was carefully evaluated by microscopic examination of serial sections through the hypothalamic region. The results indicate that lesions which completely destroyed the median eminence led to elevation in plasma prolactin and profound decreases in plasma FSH and LH associated with atrophy of testes and accessory sex organs. This result was not affected if CB154 was given to lower the elevated prolactin levels. Lesions which destroyed the rostral 2/3 of the median eminence were frequently associated with declines in plasma LH and relatively normal plasma FSH, whereas lesions which extended caudally to destroy the posterior median eminence were associated uniformly with a profound lowering of FSH. If these lesions did not include the anterior portions of the median eminence. LH levels remained normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Hypothalamic action of cachectin to alter pituitary hormone release.

Cachectin (tumor necrosis factor, TNF) is a macrophage hormone which is released during infection and after injection of bacterial lipopolysaccharides. We have already demonstrated that the peptide has direct action on the pituitary to alter pituitary hormone release in vitro. To evaluate its action in vivo, we injected it into the third ventricle (3V) of conscious, male rats and measured its effect on various anterior pituitary hormones. The peptide produced an elevation in rectal temperature measurable on first measurement at 1 hour postinjection which was maintained for 3 hours. The maximal increase in body temperature was 1-1.5 degrees C and maximal effect was obtained by a dose as low as 1 ng (0.3 pmol) of the peptide. Preinjection of indomethacin into the 3V 1 hour prior to injection of TNF completely blocked the effect on body temperature without producing an alteration in rectal temperature itself which suggests that the elevation in body temperature may be mediated by prostaglandins. Following the intraventricular injection of various doses of TNF, there was no significant effect on plasma adrenocorticotropin (ACTH) except with the highest, 100 ng dose tested, which evoked a small but significant increase in plasma ACTH with a delay of 1 to 2 hours. Thus, the dose necessary to release ACTH was much higher than that required to elevate body temperature. The effect was no longer significant in indomethacin-pretreated animals suggesting a role for prostaglandins in the effect. This highest dose of intraventricularly administered TNF also produced a relatively modest, but significant, delayed increase in plasma GH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Role of neuromedin B in the control of the release of thyrotropin in the rat.

Neuromedin B (NB), a bombesin-like peptide, was first isolated from porcine spinal cord and subsequently found in the central nervous systems of rat, cat, and human. Immunocytochemical studies have shown that NB is present in hypothalamus and various other regions of the brain and in thyrotrophs of the anterior pituitary of the rat. The possible physiological role of NB in the hypothalamic-pituitary axis is not known. Therefore, we studied the in vivo effect of this peptide on the plasma levels of thyrotropin (TSH) after administering NB to conscious freely moving adult male rats. When injected i.v., only the highest dose of NB (50 micrograms, 44.2 nmol) significantly lowered plasma TSH levels relative to levels in saline controls. When injected intraventricularly, NB doses of 0.5 and 5 micrograms (0.44 and 4.42 nmol, respectively) lowered plasma TSH levels with a 15-min latency period. Responsiveness of the pituitary to TSH-releasing hormone (TRH) was tested after the effective dose of NB was administered i.v. The increase in plasma TSH levels after the i.v. injection of 1 microgram of TRH was not altered by NB. NB at 10(-9) to 10(-7) M also reduced TSH release from hemipituitaries incubated in vitro without decreasing the response to TRH. Consequently, NB appears to have a direct inhibitory effect on TSH release from thyrotrophs. Since the response to TRH was not depressed, NB appears to act on a separate NB thyrotroph receptor that suppresses TSH release by a TRH-independent mechanism. After antiserum directed against NB was injected into the third ventricle, there was a highly significant elevation of the plasma level of TSH, beginning at 4 hr and increasing at 6 hr, relative to initial levels and levels in normal rabbit serum-injected controls. These results indicate that NB has a tonic suppressive effect on TSH release and is a physiologically significant TSH-release-inhibitory factor.

Animals↗