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S M McCann

Publications and source records attributed to S M McCann.

At least 145 records · Page 8Linked to original sources
PubMed1992

Influence of dopamine on the altered release of prolactin, luteinizing hormone, and follicle-stimulating hormone induced by interleukin-2 in vitro.

Interleukin-2 (IL-2) alters the release of anterior pituitary hormones at femtomolar concentrations from hemipituitaries incubated in vitro. This cytokine significantly lowered luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and stimulated prolactin (PRL) release, thus demonstrating a reciprocal action of the lymphokine on lactotrophs and gonadotrophs. Since dopamine (DA) is a powerful inhibitor of PRL release, in the present experiments were evaluated possible dose dependent effects of DA on IL-2-induced alterations of the release of PRL, LH, and FSH. Hemipituitaries were incubated with varying concentrations of DA, a combination of IL-2 plus DA, or a combination of haloperidol (1 x 10(-5) M) with DA for 1 h, followed subsequently by incubation with medium containing only high potassium (K+) to study the effects on depolarization-induced hormone release. DA induced a dose-related, significant lowering of the basal PRL release with a minimal effective dose (MED) of less than 19 nM. The depolarization-induced PRL release was also inhibited, but the MED was 100-fold higher than the MED to inhibit basal PRL release. DA at much higher concentrations (30, 60, and 90 microM) significantly reduced pituitary PRL content. The addition of 0.187, 3.75, 15, or 60 microM DA to IL-2-induced PRL release. IL-2 (10(-15) M) produced a significant decrease in LH and FSH release. The combination of 3.75 or 15 microM DA plus IL-2 failed to alter the IL-2 suppressed LH release, whereas the addition of 0.187 microM DA to IL-2 blocked its suppressive influence, and 60 microM DA added to Il-2 produced an additive inhibitory effect. Thus, the interaction of IL-2 and DA is biphasic on LH release. The significant reduction of FSH release induced by IL-2 was blocked in the presence of 0.187, 3.75, 15, or 60 microM DA. DA alone at relatively high concentrations of 30, 60, and 90 microM suppressed basal LH and FSH release. The effects of DA on PRL, LH, and FSH at all doses tested were blocked by the DA receptor blocker, haloperidol which by itself at the concentration tested (1 x 10(-5) M) had no effect. Thus, the actions of DA at all concentrations tested appear to be mediated via DA receptors. In conclusion, DA was capable of blocking the stimulatory action of IL-2 on PRL release and its inhibitory action on FSH release by a DA receptor mediated action.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

The effect of galanin on growth hormone-releasing factor and somatostatin release from median eminence fragments in vitro.

Galanin has been reported to stimulate secretion of GH in humans and rats. Thus, to investigate whether the effect of galanin on GH release is the result of either a stimulation of GH-releasing factor (GRF) and/or an inhibition of somatostatin (SRIF) release, we have evaluated the action of galanin on the release of SRIF and GRF from median eminence (ME) fragments in vitro. The MEs from adult male rats were incubated in Krebs-Ringer bicarbonate-glucose buffer, pH 7.4, at 37 degrees C, in an atmosphere of 95% O2, 5% CO2 with constant shaking for 30 min. Medium was discarded and replaced by medium containing various concentrations of galanin (10(-10)-10(-7) M). Galanin stimulated SRIF and GRF release in a dose-related manner. This effect was significant at concentrations varying from 10(-8) to 10(-7) M. To determine the mechanism by which galanin stimulated SRIF and GRF release, MEs were incubated with pimozide (dopaminergic blocker), phentolamine (alpha-adrenergic blocker) or naloxone (opioid blocker), at concentrations of 10(-6) M, and the effect of galanin was then evaluated. Phentolamine and naloxone did not alter the stimulatory effect of galanin, but when galanin was tested with pimozide, the galanin-induced release of SRIF and GRF was blocked. To determine whether the effect of galanin is mediated through D-1 and/or D-2 dopamine receptors, selective antagonists of D-1 (SCH 23390) and D-2 receptors (domperidone) were used (10(-7) M) in the presence of galanin (10(-7) M).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Evidence that somatostatin is localized and synthesized in lymphoid organs.

Because several peptides originally found in the pituitary as within the central nervous system have been localized in lymphoid tissues and because somatostatin (somatotropin-release-inhibiting hormone, SRIH) can act on cells of the immune system, we searched for this peptide in lymphoid organs. We demonstrated that SRIH mRNA exists in lymphoid tissue, albeit in smaller levels than in the periventricular region of the hypothalamus, the brain region that contains the highest level of this mRNA. SRIH mRNA was found in the spleen and thymus of male rats and in the spleen, thymus, and bursa of Fabricius of the chicken. Its localization in the bursa indicates that the peptide must be present in B lymphocytes since this is the site of origin of B lymphocytes in birds. The SRIH concentration in these lymphoid organs as determined by radioimmunoassay was greater in the thymus than in the spleen of the rat. These concentrations were 50 times less than those found in the periventricular region of the hypothalamus, the site of the perikarya of SRIH-containing neurons. In the chicken, as in the rat, the concentration of SRIH was greater in the thymus than in the spleen; it was present in the bursa of Fabricius, also in higher concentration than in the spleen. Fluorescence immunocytochemistry revealed the presence of SRIH-positive cells in clusters inside the white pulp and more dispersed within the red pulp of the spleen of both the rat and the chicken. The thymus from these species also contained SRIH-positive cells within the medulla and around the corticomedullary junction. In the chicken, there were large clusters of SRIH-positive cells in the medullary portion of each nodule of the bursa of Fabricius. Preabsorption of the primary antiserum or replacing this antiserum with normal rabbit serum verified the specificity of staining. Sequential immunostaining of the same sections from rat spleen using first SRIH antibody and subsequently a monoclonal antibody against a rat B-cell surface antigen revealed the presence of SRIH immunoreactivity in some, but not all, B cells. Other cell types in spleen not yet identified also stained positively with the SRIH antibody but were not reactive to monoclonal antibodies to rat Thy-1.1, a marker for all the thymic T lymphocytes. The possibility that SRIH is present in other populations of cells in the spleen cannot be ruled out. Sequential immunostaining of the same sections of rat thymus revealed the presence of SRIH immunoreactivity in a small population of T lymphocytes in the medulla, as revealed by the Thy-1.1 marker. The SRIH-positive cells were nonimmunoreactive when exposed to the B-cell marker; however, the possibility that SRIH is present in other cells was not investigated. Thus, our results indicate that SRIH is synthesized and stored in cells of the immune system. SRIH may be secreted from these cells to exert paracrine actions that alter the function of immune cells in spleen and thymus.

Animals↗
PubMed1991

Mediation of the short-loop negative feedback of luteinizing hormone (LH) on LH-releasing hormone release by melatonin-induced inhibition of LH release from the pars tuberalis.

The pineal hormone melatonin is thought to mediate the effects of the pineal gland on seasonal reproduction by altering the release of gonadotropins. The mechanism by which melatonin controls gonadotropin secretion has been obscure. Recently, labeled 2-iodomelatonin was used to localize melatonin receptors in brain by radioautography. The highest concentration of melatonin receptors was found in the pars tuberalis of the pituitary gland of mammals. Pituitary hormones, in particular luteinizing hormone (LH), have been localized in cells of the pars tuberalis. Consequently, we hypothesized that melatonin might act on its receptors in the pars tuberalis to alter the release of LH. It would then be possible for this LH to diffuse into the overlying median eminence, there to alter the release of LH-releasing hormone (LHRH) from the axons of the LHRH neurons. To evaluate this hypothesis, we incubated median eminence-pars tuberalis tissue from male rats in vitro. After preincubation in Krebs-Ringer bicarbonate buffer for 30 min, test substances were added to fresh medium and the incubation was continued for 30 min. LHRH or LH released into the medium was measured by radioimmunoassay. Melatonin induced a dose-related release of LHRH with the maximum response at the greatest concentration tested (1 microM). This concentration of melatonin also significantly reduced the release of LH into the medium. The increased release of LHRH induced by melatonin (10 microM) was completely blocked by the addition of LH (50 ng/ml), which by itself had no significant effect on LHRH release. Rat LH antiserum (final dilution, 1:1800) significantly elevated LHRH output, whereas normal rabbit serum at a similar dilution had no effect. Finally, LHRH (0.1 microM) induced a significant release of LH from median eminence-pars tuberalis tissue that was completely blocked by melatonin (10 microM). The results support the hypothesis that LH released from the pars tuberalis diffuses to the LHRH terminals in the median eminence to suppress LHRH release. Melatonin acts on its receptors in the pars tuberalis to inhibit LH release, thereby stimulating the release of LHRH from its terminals in the median eminence. The negative short-loop feedback of LH inhibits basal LHRH release in vitro since antiserum against LH increased LHRH release. The results suggest a concept concerning the mechanism by which melatonin can affect the release of pituitary hormones from the pars tuberalis. It is likely that these pituitary hormones diffuse into the median eminence to modify the release of hypothalamic releasing and inhibiting peptides, thereby altering plasma pituitary hormone concentrations.

Animals↗
PubMed1991

Interleukin 1 alpha inhibits prostaglandin E2 release to suppress pulsatile release of luteinizing hormone but not follicle-stimulating hormone.

Interleukin 1 alpha (IL-1 alpha), a powerful endogenous pyrogen released from monocytes and macrophages by bacterial endotoxin, stimulates corticotropin, prolactin, and somatotropin release and inhibits thyrotropin release by hypothalamic action. We injected recombinant human IL-1 alpha into the third cerebral ventricle, to study its effect on the pulsatile release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in conscious, freely moving, ovariectomized rats. Intraventricular injection of 0.25 pmol of IL-1 alpha caused an almost immediate reduction of plasma LH concentration; this decrease was statistically significant 20 min after injection and occurred through a highly significant reduction in the number of LH pulses, with no effect on pulse amplitude. In contrast, there was no change in pulse frequency but a small significant elevation in amplitude of FSH pulses. Intraventricular injection of the diluent had no effect on gonadotropin release. The results provide further evidence for separate hypothalamic control mechanisms for FSH and LH release. To determine the mechanism of the suppression of LH release, mediobasal hypothalamic fragments were incubated in vitro with IL-1 alpha (10 pM) and the release of LH-releasing hormone (LHRH) and prostaglandin E2 into the medium was measured by RIA in the presence or absence of norepinephrine (50 microM). IL-1 alpha reduced basal LHRH release and blocked LHRH release induced by norepinephrine. It had no effect on the basal release of prostaglandin E2; however, it completely inhibited the release of PGE2 evoked by norepinephrine. To evaluate the possibility that IL-1 alpha might also interfere with the epoxygenase pathway of arachidonic acid metabolism, epoxyeicosatrienoic acids were also measured. IL-1 alpha had no effect on the content of epoxyeicosatrienoic acids in the hypothalamic fragments as measured by gas chromatography and mass spectrometry. In conclusion, IL-1 alpha suppresses LH but not FSH release by an almost complete cessation of pulsatile release of LH in the castrated rat. The mechanism of this effect appears to be by inhibition of prostaglandin E2-mediated release of LHRH.

Animals↗
PubMed1991

Lesions of the hypothalamus and pituitary inhibit volume-expansion-induced release of atrial natriuretic peptide.

Expansion of the blood volume causes a release of atrial natriuretic peptide (ANP) that is believed to be important in induction of the subsequent natriuresis and diuresis which, in turn, acts to reduce the increase in blood volume. Since stimulation of the anteroventral portion of the third cerebral ventricle (AV3V) induced a rapid elevation of plasma ANP, whereas lesions of the AV3V were followed by a marked decline in plasma concentration of the peptide, we hypothesized that release of ANP from the brain ANP neuronal system might be important to the control of plasma ANP. The perikarya of the ANP-containing neurons are densely distributed in the AV3V and their axons project to the median eminence and neural lobe. To test the hypothesis that these neurons are involved in volume-expansion-induced ANP release, by using electrolysis we destroyed the AV3V, the site of the perikarya, in male rats. Other lesions were made in the median eminence and posterior pituitary, sites of termination of the axons of these neurons, and also hypophysectomy was performed in other animals. In conscious freely moving animals, volume expansion and stimulation of postulated sodium receptors in the hypothalamus were induced by injection of hypertonic NaCl solution [0.5 or 0.3 M NaCl; 2 ml/100 g (body weight)]. Volume expansion alone was induced with the same volume of an isotonic solution (NaCl or glucose). In the sham-operated rats, volume expansion with hypertonic or isotonic solutions caused equivalent rapid increases in plasma ANP that peaked at 5 min and returned nearly to control values by 15 min. Lesions caused a decrease in the initial levels of plasma ANP on comparison with values from the sham-operated rats, and each type of lesion induced a highly significant suppression of the response to volume expansion on testing 1-5 days after lesions were made. Because a common denominator of the lesions was elimination of the brain ANP neuronal system, these results suggest that the brain ANP plays an important role in the mediation of the release of ANP that occurs after volume expansion. Since the content of ANP in this system is much less than that in the atria, there must be a remarkable increase in synthesis and release of brain ANP associated with this stimulus. It is also possible that blockade of volume-expansion-induced release of other neurohypophyseal hormones, such as endothelin, may block release of ANP from atrial myocytes. It is probable that volume expansion detected by stretch of atrial and carotid-aortic baroreceptors causes afferent input to the brain ANP system, thereby causing increased release of the peptide from the median eminence and neural lobe. Our results emphasize the importance of brain ANP to the control of ANP release to the blood.

Animals↗
PubMed1991

Anterior pituitary hormone control by interleukin 2.

Several monokines, proteins secreted by monocytes and macrophages, alter release of hormones from the anterior pituitary. We report here the ability of femtomolar concentrations of interleukin 2 (IL-2), a lymphokine released from T lymphocytes, to alter directly pituitary hormone release. The effects of concentrations of IL-2 ranging from 10(-17) to 10(-9) M on anterior pituitary hormone release were evaluated in vitro. Hemipituitaries were preincubated in 1 ml of Krebs-Ringer bicarbonate buffer (KRB) followed by incubation for 1 or 2 hr with KRB or KRB containing different concentrations of IL-2. This was followed by incubation for 30 min in 56 mM potassium medium to study the effect of pretreatment with IL-2 on subsequent depolarization-induced hormone release. Prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), corticotropin (ACTH), growth hormone (GH), and thyrotropic hormone (TSH) released into the incubation medium were measured by radioimmunoassay. IL-2 stimulated the basal release of PRL at 1 or 2 hr but suppressed the subsequent depolarization-induced PRL release, perhaps because the readily releasable pool of PRL was exhausted. The minimal effective dose (MED) was 10(-15) M. Conversely, IL-2 significantly suppressed the basal release of LH and FSH at 1 or 2 hr, with a MED of 10(-16) M, thus demonstrating a reciprocal action of the cytokine on lactotrophs and gonadotrophs. The subsequent depolarization-induced release of LH and FSH was suppressed, indicative of a persistent inhibitory action of IL-2. IL-2 stimulated ACTH and TSH release at 1 hr and the MEDs were 10(-12) and 10(-15) M, respectively. Conversely, IL-2 significantly lowered the basal release of GH at 1 hr, with a MED of 10(-15) M. The release of GH was not altered at 2 hr. The high potassium-induced release of ACTH, TSH, and GH was not affected. The results demonstrate that IL-2 at picomolar concentrations affects the release of anterior pituitary hormones. This cytokine may serve as an important messenger from lymphocytes exerting a direct paracrine action on the pituitary by its release from lymphocytes in the gland or concentrations in the blood that reach the gland may be sufficient to activate it.

Adrenocorticotropic Hormone↗
PubMed1991

Rat growth hormone-releasing factor stimulates cyclic GMP formation and phosphatidylinositol metabolism in the median eminence.

The effects of rat growth hormone releasing factor (rGRF) on somatostatin (SRIF) secretion, cyclic nucleotide production and phosphatidylinositol metabolism were investigated in the median eminence (ME), using an in vitro system. Medium was discarded and replaced by medium containing various concentrations of rGRF or rGRF plus epinephrine (E, 6 x 10(-7) M). rGRF had no effect on basal or E-stimulated release of cAMP. In the same experiments rGRF markedly stimulated SRIF release. These results suggested that cAMP is not involved in the stimulatory effect of GRF on SRIF release. However, GRF significantly stimulated release of both SRIF and cGMP in a dose-related manner. Maximal stimulation was observed at 10(-10) M GRF (p less than 0.005) which also produces maximal SRIF release. 2'0-monobutyrylguanosine 3'5' cyclic phosphate (mbcGMP, 10(-11) to 10(-10) M) stimulated SRIF release from ME fragments (p less than 0.001 at 10(-10) M) whereas the control, sodium butyrate (10(-6) M), had no effect. GRF caused significant elevation of 30.6% in the concentration of labelled inositol phosphates [( 3H]-IPs) in the ME. These data indicate that GRF stimulation of SRIF release is accompanied by increased cGMP production and phosphatidyl-inositol (PI) metabolism but does not alter cAMP production. Because mbcGMP can directly stimulate SRIF release, we suggest that GRF causes a receptor-mediated increase in the metabolism of phosphatidylinositol and cGMP formation. These actions therefore may be among the early metabolic events in the mechanism of GRF-stimulated SRIF release from the ME.

Animals↗
PubMed1991

Feedback of follicle-stimulating hormone to inhibit luteinizing hormone and stimulate follicle-stimulating hormone release in ovariectomized rats.

Injection of ovine follicle-stimulating hormone (o-FSH) into the third cerebral ventricle significantly suppressed plasma luteinizing hormone (LH) release in conscious, unrestrained ovariectomized rats. Intraventricular injection of o-FSH (0.5 microgram) significantly lowered the plasma levels of LH by 70 min and decreased pulse frequency, whereas the pulsatile release of FSH was unchanged during the 180-min duration of the experiment. In a 12-hour experiment, the suppression of LH release reached the maximum within 3 h (p less than 0.001), followed by a return of plasma LH level to initial values 6-8 h after intraventricular injection of o-FSH at doses of 0.5, 4 and 8 micrograms. Plasma levels of FSH were not significantly changed by the low dose of o-FSH (0.5 microgram), but there was a delayed elevation of plasma FSH during the 8-12 h after intraventricular injection of o-FSH at higher doses (4 and 8 micrograms). On the other hand, plasma prolactin was unchanged after intraventricular injection of o-FSH. Since the pituitary responsiveness to synthetic LH-releasing hormone (LHRH) was unimpaired at the end of the sampling and incubation with o-FSH suppressed the release of LHRH from median eminence terminals, these data indicate that FSH acts intrahypothalamically to suppress LHRH release. The late elevation of plasma FSH may be the result of enhanced release of FSH-releasing factor or of a delayed, direct effect of the hormone on the gonadotropes to increase release of FSH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

The effect of interleukin-6 on pituitary hormone release in vivo and in vitro.

Intravenously administered interleukin-6 (IL-6), a monokine produced by activated monocytes and folliculostellate cells of the pituitary gland, has been recently reported to elevate plasma ACTH level and to stimulate PRL, GH and LH release from cultured pituitary cells. To determine the site(s) of action of IL-6 in the control of pituitary hormone release, we injected human recombinant IL-6 into the third brain ventricle (3V) of freely moving, conscious male rats. Both 0.05 and 0.25 pmol doses of IL-6 were ineffective to change plasma ACTH in comparison to the values in controls. The maximal IL-6 dose tested of 1.25 pmol increased plasma ACTH within 15 min and the response lasted over 180 min. Plasma TSH levels were significantly lowered by a dose of 0.25 pmol IL-6, but neither the lower dose of 0.05 pmol nor the higher dose of 1.25 pmol altered plasma TSH levels throughout the 180 min of the experiment. Plasma PRL and GH levels were not changed by any IL-6 dose tested. In ovariectomized rats plasma LH and FSH levels were also unaltered by IL-6. The effects of IL-6 on plasma ACTH and TSH were only partially paralleled by increased rectal temperature which suggests that hypothalamic temperature regulating centers were independent of these actions. To evaluate a possible direct effect on the pituitary, IL-6 was incubated in vitro with hemipituitaries under an atmosphere of 95% O2/5% CO2. After 1 h of incubation IL-6 failed to cause any change in the secretion of pituitary hormones throughout a concentration range of 10(-15)-10(-9) M.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1991

Effect of medial zona incerta lesions on the ovulatory surge of gonadotrophins and prolactin in the rat.

Bilateral electrolytic lesions of the incertohypothalamic A13 dopamine (DA) system were made on the morning of proestrus in female rats with regular estrous cycles under ether anesthesia. Hourly blood samples were withdrawn, via a jugular catheter from conscious, freely moving rats, between 14.00 h and 18.00 h on the afternoon of proestrus. Plasma LH, FSH and prolactin levels were determined by RIA. The preovulatory surges of LH and prolactin were blocked in animals in which the A13 DA nucleus was destroyed by more than 70%. Levels of FSH were not significantly different from those of control of sham-lesioned groups. Lesions that were dorsal, ventral or caudal to the A13 DA systems did not affect the preovulatory surges of LH and prolactin whereas anterior lesions caused variable changes in the level of all three hormones. These data suggest that the A13 DA region may have a role in the control of the preovulatory surges of LH and prolactin.

Animals↗
PubMed1991

Roles of somatostatin and growth hormone-releasing factor in ether stress inhibition of growth hormone release.

In order to evaluate the release of somatostatin (SRIF) and growth hormone-releasing factor (GRF) into the pituitary gland in response to ether stress, a push-pull perifusion (PPP) technique has been used in freely moving rats. Push-pull cannulae (PPC) were implanted into the anterior pituitary (AP) glands of male rats. After a 7-day recovery period the rats were fitted with indwelling jugular catheters. The next day the animals were subjected to PPP of the AP during 1 h followed by ether stress (2 min) and another hour of perifusion. The perifusion flow was 20 microliters/min and 10-min fractions were collected and assayed for SRIF and GRF by RIA. Plasma growth hormone (GH) levels were assayed every 10 min. At the end of the experiments, the accuracy of PPC tip placements was ascertained with a dissecting microscope. Under basal conditions there were 2.9 pulses/h of SRIF with an amplitude of 12.76 +/- 0.46 pg. The output of SRIF and GRF in the 10-min period beginning with application of ether was increased 2-fold (p less than 0.005 and p less than 0.01, respectively). Interestingly, the increased release of SRIF continued for an additional 10 min, whereas GRF output decreased and was almost undetectable. The release of both GRF and SRIF had returned to basal values 20-30 min after stress. Mean plasma GH levels were significantly lowered 10 min after stress. Each of the 9 animals showed a restoration of pulsatile GH release to basal levels within 20-30 min after stress. Our findings provide compelling evidence that SRIF plays a prominent role in stress-induced inhibition of GH release in the rat by blocking the response to the transient elevation of GRF and continuing to suppress GH release for 20 min.

Animals↗
PubMed1991

The effect of tubero-infundibular dopaminergic neurons on prolactin and alpha-melanocyte stimulating hormone release.

The effect of tubero-infundibular dopaminergic neurons (TIDA) on the release of prolactin (PRL) and alpha-melanocyte stimulating hormone (alpha-MSH) was studied in median eminence-lesioned (MEL) male rats (N = 6-28). Plasma PRL and alpha-MSH levels were significantly elevated 2 (86.1 +/- 19.8 and 505.1 +/- 19.1 ng/ml), 4 (278.7 +/- 15.5 and 487.4 +/- 125.1 ng/ml), 7 (116.2 +/- 16.2 and 495.8 +/- 62.6 ng/ml) and 14 (247.3 +/- 26.1 and 448.4 +/- 63.8 ng/ml) days after MEL when compared to sham-operated control animals (55.5 +/- 13.4 and 56.2 +/- 6.1 ng/ml, respectively). MEL altered plasma PRL and alpha-MSH levels in a differential manner, with a 1.5- to 5.0-fold increase in PRL and an 8.0- to 9.0-fold increase in alpha-MSH. The increase of alpha-MSH levels occurred abruptly and remained constant from days 2 to 14. These observations indicate that TIDA plays an important role in the pituitary release of PRL and alpha-MSH and provide evidence that the release of the two hormones occurs in a differential manner.

Animals↗
PubMed1990

Role of monokines in control of anterior pituitary hormone release.

It has long been known that endogenous pyrogen, released as a result of injection of typhoid vaccine or in response to infection, produces fever and increases ACTH secretion. Recent studies have indicated that endogenous pyrogen is, at least in part, IL-1. This monokine has now been shown to activate the release of ACTH by a hypothalamic mechanism with release of CRF and possibly vasopressin, which stimulates the corticotrophs. There may also be a pituitary action to stimulate the release of ACTH directly. In our experiments we showed that IL-1 at low but not higher doses appears to act intrahypothalamically to stimulate GH and PRL release and to inhibit TSH release. In the meantime, another monokine, cachectin, was isolated and its structure determined. We have found that this monokine can act following its third ventricular injection to stimulate ACTH, PRL, and GH release and to inhibit TSH release, at least in part, by release of prostaglandins since indomethacin, an inhibitor of prostaglandin synthesis, produced a blockade of the responses except for those of ACTH. This peptide also has highly potent effects to alter pituitary hormone release by direct action on the pituitary to stimulate ACTH, GH, and TSH and to a slight extent PRL release. These actions appear to involve prostaglandins since indomethacin blocks all of the effects except for the effect on ACTH secretion. This monokine also produces a dose-related lowering of anterior pituitary cyclic AMP levels. When the monokine was incubated along with somatostatin, the lowering of cyclic AMP was reversed, and a potent PRL-releasing effect of the monokine was visible. We have begun studies with a third monokine, gamma interferon, which indicate that it stimulates ACTH release but suppresses plasma GH and TSH levels by a hypothalamic action. It is apparent that these various monokines have powerful effects to alter hypothalamic-pituitary function and that they probably mediate most of the effects of infections on the release of anterior pituitary hormones.

Animals↗
PubMed1990

Selective FSH-releasing activity of [D-Trp9]GAP1-13: comparison with gonadotropin-releasing abilities of analogs of GAP and natural LHRHs.

We had previously shown that fragments of human gonadotropin-releasing hormone associated peptide (GAP) stimulated FSH and LH release in vivo. In particular, GAP1-13 had a preferential FSH-releasing activity. To decrease enzymatic degradation, analogs of GAP1-13 with D-amino acid substitutions were synthesized. The activities were tested in ovariectomized, estrogen-progesterone primed (OEP) rats and compared with those of GAP1-13, mammalian (m), chicken II (cII), and lamprey (1) LHRH. The peptides were injected (IV) into conscious, OEP rats and blood samples were obtained via the jugular catheter. [D-Trp9 )GAP1-13 selectively stimulated FSH release at a dose of 1 microgram. Multiple injections of this analog (10 micrograms every 30 min for 5 injections) induced a marked elevation of plasma FSH values which peaked (p less than 0.001) after the third injection. By contrast, [D-Trp9]GAP1-13 had no effect on LH and prolactin (PRL) release after either single or multiple injections. These doses of [D-Ala4]GAP1-13 had no effect on the release of FSH, LH or PRL. Both human GAP1-13 and its [D-Trp9] analog exerted a selective FSH-releasing effect at a dose of 10 micrograms, however, the [D-Trp9] analog was more potent than GAP1-13 on FSH release. The potency of [D-Trp9]GAP1-13 in releasing FSH was approximately 1/100th that of mLHRH. Chicken II LHRH had slightly selective FSH-releasing activity with a potency 1/10th that of mLHRH. Lamprey LHRH had a preferential LH-releasing activity and a potency 1000 times less than mLHRH. In conclusion. [D-Trp9]GAP1-13 is a selective FSH-releasing peptide of potential clinical value.

Animals↗
PubMed1990

In vitro effect of delta 9-tetrahydrocannabinol to stimulate somatostatin release and block that of luteinizing hormone-releasing hormone by suppression of the release of prostaglandin E2.

Previous in vivo studies have shown that delta 9-tetrahydrocannabinol (THC), the principal active ingredient in marijuana, can suppress both luteinizing hormone (LH) and growth hormone (GH) secretion after its injection into the third ventricle of conscious male rats. The present studies were designed to determine the mechanism of these effects. Various doses of THC were incubated with either stalk median eminence fragments (MEs) or mediobasal hypothalamic (MBH) fragments in vitro. Although THC (10 nM) did not alter basal release of LH-releasing hormone (LHRH) from MEs in vitro, it completely blocked the stimulatory action of dopamine or norepinephrine on LHRH release. The effective doses to block LHRH release were associated with a blockade of synthesis and release of prostaglandin E2 (PGE2) from MBH in vitro. In contrast to the suppressive effect of THC on LHRH release, somatostatin release from MEs was enhanced in a dose-related manner with a minimal effective dose of 1 nM. Since PGE2 suppresses somatostatin release, this enhancement may also be related to the suppressive effect of THC on PGE2 synthesis and release. We speculate that these actions are mediated by the recently discovered THC receptors in the tissue. The results indicate that the suppressive effect of THC on LH release is mediated by a blockade of LHRH release, whereas the suppressive effect of the compound on growth hormone release is mediated, at least in part, by a stimulation of somatostatin release.

Animals↗