Biomedical subjects

A Torsello

Publications and source records attributed to A Torsello.

54 records · Page 3Linked to original sources

PubMed1996

Role of the neuronal histaminergic system in the regulation of somatotropic function: comparison between the neonatal and the adult rat.

To study possible age-related differences in the role of neuronal histaminergic pathways in the control of GH secretion, the effects of alpha-fluoromethylhistidine (alpha-FMH), an irreversible inhibitor of histamine (HA) synthesis, were examined on basal and opioid-induced GH release in neonatal and adult rats. The mechanisms involved in such effects were evaluated by measuring pituitary GH mRNA levels and hypothalamic levels of GH-releasing hormone (GHRH) and somatostatin (SRIF) mRNAs. Daily injection of alpha-FMH (20 mg/kg, s.c.) in pups of either sex, from birth until 10 days of age, caused a significant increase in baseline plasma GH and potentiated the GH response to the [Met5]-enkephalin analog FK 33-824 (1 mg/kg, s.c.) administered 3 h after the last alpha-FMH injection. GH and SRIF mRNA levels were significantly higher in alpha-FMH-treated pups than in controls, whereas no difference was observed in GHRH mRNA levels. In young adult male rats, acute administration of alpha-FMH (100 mg/kg, s.c., 3 h before) did not change significantly basal GH levels but potentiated FK 33-824 (0.3 mg/kg, intracarotid)-induced stimulation of GH secretion. Repeated administration of alpha-FMH (200 micrograms/rat, i.c.v., for 3 days) failed to modify basal and FK 33-824-induced GH secretion, caused a significant reduction in hypothalamic GHRH mRNA levels and left SRIF and GH mRNAs unchanged. These findings indicate that HA exerts an inhibitory effect on GH secretion in both neonatal and adult rats. The different effects of short-term HA depletion on hypothalamic and pituitary indices of somatotropic function observed at the two age periods may be ascribed to the immaturity of the HA system in early postnatal life and to a different functional role of GH-regulatory factors during ontogeny.

Aging↗

PubMed1995

Somatotropic dysregulation in old mammals.

In old mammals, including humans, the spontaneous growth hormone (GH) secretory pattern is markedly reduced resulting in lower amounts of GH released over 24 h, and the GH response to administration of GH-releasing hormone (GHRH) is reduced. In agreement with these in vivo findings, an impaired responsiveness to GHRH is evident in the pituitary of old male and female rats in vitro, and this is linked with a diminished stimulation of adenylate cyclase by GHRH. The poor GH responsiveness to GHRH in old mammals, which in the rat is coupled to a defective number of GHRH receptors in the somatotrophs, is likely due to a primary deficiency of GHRH availability, as implied by the diminished GHRH immunoreactivity and gene expression in and GHRH release from the hypothalamus of old rats. Attempts have been made to stimulate the sluggish somatotrophic function in elderly humans and dogs using GHRH; in either species positive results were obtained though, overall, it would seem that the GHRH hypofunction does not entirely account for the GH hyposecretory state during ageing. Concerning somatostatin, although the expression of this peptide decreases with age in the rat hypothalamus, secretion and activity of this hormone is increased, resulting in an altered relationship between GHRH and somatostatin gene expression and secretion. It is likely that defects, especially in catecholaminergic and cholinergic neurons, are instrumental in altering specific peptidergic neurons. Reportedly, catecholamines induce GH release by stimulating GHRH neurons and inhibiting somatostatin-releasing neurons; acetylcholine stimulates GH release via muscarinic receptors, in this way inhibiting the action of somatostatin neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1995

Involvement of brain catecholamines and acetylcholine in growth hormone hypersecretory states. Pathophysiological, diagnostic and therapeutic implications.

Secretion of growth hormone (GH) is excessive in acromegaly, but also in a number of other pathological states such as anorexia nervosa, insulin-dependent diabetes mellitus (IDDM), liver cirrhosis, depression, renal failure and GH-insensitivity syndrome. Abnormalities in the neuroendocrine control of GH secretion and/or a state of insensitivity to GH contribute to hypersecretion of GH in these states, with the possible exception of acromegaly, which appears to be a primary pituitary disease. GH hypersecretion may also occur in neonates or adolescents with tall stature, thus reflecting particular physiological or paraphysiological conditions. In the cohort of brain neurotransmitters, catecholamines and acetylcholine reportedly play a major role in the control of neurosecretory GH-releasing hormone (GHRH) and somatostatin (SS)-producing neurons, and hence GH secretion. Activation of alpha 2-adrenoceptors or of muscarinic cholinergic receptors in the hypothalamus stimulates GH release, probably through stimulation of GHRH and inhibition of SS release, respectively. Activation of dopamine receptors likewise stimulates GH release, while activation of beta-receptors inhibits GH release through stimulation of hypothalamic SS function. This review discusses the involvement of brain catecholamines and acetylcholine in GH hypersecretory states, including anorexia nervosa, acromegaly, IDDM, liver cirrhosis, depression, renal failure and GH insensitivity syndrome, with a view to providing a fuller understanding of their pathophysiology and, whenever possible, diagnostic and therapeutic implications.

Acetylcholine↗

PubMed1994

GH-releasing activity of Hexarelin, a new growth hormone releasing peptide, in infant and adult rats.

In recent years several synthetic peptides have been shown to be active in inducing GH secretion in different mammalian species. Among them GHRP-6, GHRP-1 and GHRP-2 have demonstrated high effectiveness and high selectivity in stimulating GH release. In the present paper we report studies on the GH-secreting properties of a GHRP analog in which Trp was substituted with the chemically more stable 2-Methyl-Trp. In studies performed in conscious 10-day old rats, the hexapeptide Hexarelin (His-D-2Me-Trp-Ala-Trp-D-Phe-Lys-NH2) resulted very active in stimulating GH secretion. In anesthetized adult male rats, i.v. administration of GHRP-6 or Hexarelin elicited prompt GH release with peak GH levels occurring within 10 min At all the doses tested, the 2 peptides possessed similar effectiveness in stimulating GH release. Hexarelin given s.c. elicited a long-lasting GH release and was slightly more effective than GHRP-6. In conclusion, these findings indicate that Hexarelin is a highly effective GH releaser and might represent a valuable diagnostic and/or therapeutic tool in clinical practice.

Aging↗

PubMed1994

Growth hormone-releasing hexapeptide is a potent stimulator of growth hormone gene expression and release in the growth hormone-releasing hormone-deprived infant rat.

The growth hormone-releasing hexapeptide (GHRP-6) specifically stimulates growth hormone (GH) secretion in several animal species and humans. The mechanism of action of GHRP-6 is largely unknown, although experimental evidence indicates that it may modulate growth hormone-releasing hormone (GHRH) and somatostatin actions at the pituitary or hypothalamic level. To gain more insight into the mechanism(s) of action of GHRP-6, we studied the infant rat, an animal model highly responsive to GH-releasing stimuli. In 14-d-old rats GHRP-6 (32-600 micrograms/kg, s.c.) induced a marked and dose-dependent rise in plasma GH concentrations, maximal stimulation occurring with the dose of 300 micrograms/kg. Neither GHRH nor somatostatin antiserum prevented or modified the GH release elicited by GHRP-6. In pups passively immunized with GHRH antibodies, a 5-d treatment with GHRP-6 (80 micrograms/kg, s.c., twice daily) completely counteracted the inhibitory effect of GHRH deprivation on GH mRNA expression. In vitro GHRP-6 (10(-7) and 10(-6) M) induced a small and transient stimulation of GH release from cultured pituitary cells. These results indicate the following: 1) GHRP-6 is a potent stimulator of GH release in rat pups; 2) it stimulates GH gene expression in the GHRH-deprived pup; 3) during the neonatal period its action is not mediated by GHRH or somatostatin; and 4) its actions are not directed at the somatotrophs.

Animals↗

PubMed1994

Somatotropic dysfunction in growth hormone-releasing hormone-deprived neonatal rats: effect of growth hormone replacement therapy.

In a previous work, we reported that passive immunization with anti-growth hormone-releasing hormone (GHRH) antibodies (GHRH-Ab) in neonatal rats caused disruption of somatotropic function that was still present 60 d posttreatment. We studied the reversibility of this condition by growth hormone (GH) replacement therapy. Neonatal rats received GHRH-Ab (50 microL/rat, s.c.) or normal rabbit serum every second day from birth up to postnatal d 10 and received hGH (0.4 microgram/g body weight, s.c., b.i.d.) or vehicle in a 2 x 2 factorial design. Animals were studied on d 11 of age. In GHRH-Ab-treated rats, GH therapy 1) counteracted the reduced body weight and low plasma IGF-I levels; 2) failed to modify the reduced pituitary weight and GH content; 3) further reduced the low plasma GH levels; 4) partially restored the defective GH responsiveness to GHRH; 5) failed to modify the reduced hypothalamic somatostatin and increased GHRH gene expression in the hypothalamus; and 6) reverted the decreased pituitary somatostatin binding. Morphologic and morphometric evaluation of the pituitary gland from GHRH-AB+GH pups showed that the number of GH-labeled structures was lower than in normal rat serum-GH-treated pups, whereas the total GH immunoreactivity per unit surface, an index of intracellular hormone concentration, was slightly higher than in vehicle-GH or GHRH-Ab pups. As determined by electron microscopy, somatotropes from GHRH-Ab+GH pups had morphologic features of high cellular activity. It appears that in GHRH-deprived pups GH replacement therapy can normalize most but not all altered indices of the somatotropic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Long-term changes of somatotrophic function induced by deprivation of growth hormone-releasing hormone during the fetal life of the rat.

We have studied the effects of intra-amniotic administration of an anti-GH-releasing hormone serum (GHRH-Ab) on day 16 of fetal life in the rat, when the ontogenetic development of the GHRH neuronal system occurs. Control animals received normal rabbit serum. Following delivery, body weight was monitored for the next 30 days as an index of somatic growth, and the following indices of somatotrophic function were determined: plasma and pituitary GH, pituitary GH mRNA, hypothalamic GHRH and somatostatin mRNA, and the in vivo GH responsiveness to GHRH. At birth, GHRH-Ab-treated rats had a body weight that was equivalent to that of control rats but, starting from postnatal day 6 up to day 30, they had a significantly reduced body weight. Pituitary weight, the absolute pituitary GH content and GH mRNA levels were lower in experimental compared with control rats, while pituitary GH concentrations were similar in the two groups, thus implying that there was a defect, not only in GH synthesis, but also in GH release. In agreement with this theory, basal GH levels and GHRH-stimulated GH secretion were reduced in GHRH-Ab-treated rats but, in contrast, hypothalamic regulation of GH secretion appeared to be working in these rats as they were still able to respond to the low plasma GH by increasing GHRH and decreasing somatostatin mRNA levels. These findings indicate that deprivation of GHRH during fetal life induces long-lasting changes of growth rate and somatotrophic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Calcium signaling and secretory responses in agonist-stimulated pituitary gonadotrophs.

In cultured pituitary gonadotrophs, gonadotropin-releasing hormone (GnRH) caused dose-dependent and biphasic increases in cytoplasmic calcium concentration ([Ca2+]i) and LH release. Both extra- and intracellular calcium pools participate in GnRH-induced elevation of [Ca2+]i and LH secretion. The spike phase of the [Ca2+]i response represents the primary signal derived predominantly from the rapid mobilization of intracellular Ca2+. In contrast, the prolonged phase of the Ca2+ signal depends exclusively on Ca2+ entry from the extracellular pool. The influx of Ca2+ occurs partially through dihydropyridine-sensitive calcium channels. Both [Ca2+]i and LH responses to increasing concentrations of GnRH occur over very similar time scales, suggesting that increasing degrees of receptor occupancy are transduced into amplitude-modulated Ca2+ responses, which in turn activate exocytosis in a linear manner. However, several lines of evidence indicated the complexity over the relationship between Ca2+ signaling and LH exocytosis. In contrast to [Ca2+]i measurements in cell suspension, single cell Ca2+ measurements revealed the existence of a more complicated pattern of Ca2+ response to GnRH, with a biphasic response to high agonist doses and prominent oscillatory responses to lower GnRH concentrations, with a log-linear correlation between GnRH dose and the frequency of Ca2+ spiking. In addition, analysis of the magnitudes of the [Ca2+]i and LH responses of gonadotrophs to a wide range of GnRH concentrations in the presence and absence of extracellular Ca2+, and to K+ and phorbol ester stimulation, showed non-linearity between these parameters with amplification of [Ca2+]i-mediated exocytosis. Studies on cell depleted of protein kinase C under conditions that did not change the LH pool suggested the participation of protein kinase C in this amplification, especially during the plateau phase of the secretory response to GnRH.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1992

Tissue-specific regulation of vasoactive intestinal peptide messenger ribonucleic acid levels by estrogen in the rat.

The early and chronic effects of 17 beta-estradiol on vasoactive intestinal peptide (VIP) gene expression in rats were examined. Total RNA of four VIP-producing tissues were subjected to Northern blot analysis 15 and 30 min, and 1, 3, 6, and 24 h after a single injection of 17 beta-estradiol (100 micrograms/kg ip). Pituitary, hypothalamus, brain, and ileum VIP messenger RNA (mRNA) levels rose in a time-dependent manner after estrogen treatment. In the pituitary, the increase was maximal at 30-60 min, whereas in the hypothalamus, the increase reached significance only at 3 h but then persisted until at least 24 h. In the brain, a transient increase in VIP mRNA was observed at 30 min, whereas VIP mRNA levels in the ileum responded in a biphasic pattern; the initial early increase was followed by a second elevation occurring at 6 h. A smaller 1-kilobase VIP-related transcript particularly abundant in the pituitary was regulated in parallel with the 1.7-kilobase mature VIP mRNA species. Continuous estrogen stimulation for 7 weeks dramatically increased both mRNA species in the pituitary but did not affect VIP mRNA levels in the other tissues. These data suggest that the regulation of VIP gene expression by transient increases in estrogen levels is rapid and that the pattern of induction is tissue specific.

Animals↗

PubMed1992

Steroids and tissue-specific modulation of galanin gene expression in the male rat reproductive system.

Galanin is a neuropeptide widely distributed throughout the vertebrate neural and endocrine system. Galanin can influence pituitary hormone secretion, intestinal motility, and other biological activities. The precise physiological role of galanin is unknown. We studied the control of galanin gene expression in peripheral organs in the male rat using Northern blot and in situ hybridization techniques. In the adrenals and prostate, galanin mRNA was undetectable in the controls and did not change after the administration of dexamethasone (0.0001-10.0 mg/kg, ip) and diethylstilbestrol (0.1 mg/kg, ip). In the testis, thymus, seminal vesicles, medial basal hypothalamus, and colon, galanin message was detectable, but was not influenced by steroids. On the other hand, dexamethasone (0.5-10.0 mg/kg) was very effective in enhancing galanin expression in the vas deferens and epididymis (4- to 7-fold in the vas deferens), with a peak 6-9 h after the treatment. Diethylstilbestrol (0.1 mg/kg) stimulated galanin mRNA transcription only in the vas deferens (2- to 3-fold), with a peak 1-3 h after the treatment. Dihydrotestosterone treatment (0.2-0.4 mg/kg) was ineffective in all tissues examined. In the vas deferens and seminal vesicles, galanin mRNA has been localized at a cellular level by in situ hybridization. In these tissues only fibroblast-like cells contained the message. These data demonstrate that galanin is expressed in the male rat reproductive system and that steroid hormones participate in the control of galanin gene expression in a tissue- and hormone-specific fashion.

Adrenal Glands↗

PubMed1991

Interactions between calcium and protein kinase C in the control of signaling and secretion in pituitary gonadotrophs.

Single pituitary gonadotrophs exhibit episodes of spontaneous fluctuations in cytoplasmic calcium concentration [( Ca2+]i) due to entry through voltage-sensitive calcium channels (VSCC) and show prominent agonist-induced oscillations in [Ca2+]i that are generated by periodic release of intracellular Ca2+. Gonadotropin releasing hormone (GnRH) elicited three types of Ca2+ responses: at low doses, subthreshold, with an increase in basal [Ca2+]i; at intermediate doses, oscillatory, with dose-dependent modulation of spiking frequency; and at high doses, biphasic, without oscillations. Elevation of [Ca2+]i or activation of protein kinase C (PKC) did not influence the frequency of agonist-induced [Ca2+]i spikes but caused dose-dependent reductions in amplitude for all types of Ca2+ response. Stimulation of transient Ca2+ spikes by GnRH was followed by inhibition of the spontaneous fluctuations. GnRH also reduced the ability of high extracellular K+ to promote Ca2+ influx through VSCC. Activation of PKC by phorbol esters stimulated Ca2+ influx in quiescent cells but inhibited influx when VSCC were already activated, either spontaneously or by high K+. In contrast to their biphasic actions on [Ca2+]i, phorbol esters exerted only stimulatory actions on gonadotropin release, even when Ca2+ influx was concomitantly reduced. However, pituitary cells had to be primed with an appropriate [Ca2+]i level before exocytosis could be amplified by PKC. In PKC-depleted cells, all actions of phorbol esters on Ca2+ entry and amplitude modulation, and on LH release, were abolished. GnRH-induced LH secretion was also significantly reduced, especially the plateau phase of the response. These data indicate that Ca2+ and PKC serve as interacting signals during the cascade of cellular events triggered by agonist stimulation, in which Ca2+ turns cell responses on or off, and PKC amplifies the positive and negative effects of Ca2+.

Alkaloids↗

PubMed1991

Galanin.

Explore the source record for details and available documents.

Animals↗

PubMed1990

Age-dependent modulation by galanin of growth hormone release from rat pituitary cells in culture.

The effect of galanin (Gal), a 29-amino acid peptide widely distributed in mammalian CNS, was investigated in cultured pituitary cells of rats of different ages. Gal (0.1-10/microM) stimulated GH release in a concentration-dependent manner in 5-and 10-day-old rat pituitaries (EC50: 0.87 and 1.73/microM, respectively) but was ineffective (0.01-1/microM) or even inhibitory (10/microM) in 40-day-old male rat pituitaries. Gal (0.1-10/microM) was ineffective to alter stimulation of GH release induced by GHRH (10 nM) in 5-day-and 40-day-old rat pituitary cells, but Gal (1/microM) slightly inhibited (24%) it in 10-day-old rat pituitaries. Gal (1 and 10/microM) also inhibited GH secretion (45 and 58%, respectively) from 40-day-old pituitary cells when a lower GHRH dose (0.1 nM) was used for stimulation. The results of this study indicate that Gal has the ability to either stimulate or inhibit GH release from dispersed pituitary cells and that its effects are closely related to the age of the rats.

Aging↗

PubMed1990

Age-related modulatory activity by a cholinergic agonist on the growth hormone response to GH-releasing hormone in the rat.

The involvement of the cholinergic system in growth hormone (GH) secretion has acquired increased importance in the last few years. In rats, pretreatment with muscarinic cholinergic agonists potentiates the GH release induced by GH-releasing hormone (GHRH), via inhibition of somatostatin (SRIF) release from the hypothalamus. The aim of this study was to validate the use of cholinergic agonists to probe the functional activity of the hypothalamic SRIF system. It is known that hypothalamic SRIF displays an age-related increase in its functional activity; therefore, rats from 10 days to 29 months of age were used and challenged with GHRH following acute administration of pilocarpine, a cholinergic muscarinic agonist. Following administration of GHRH alone there was an age-related decline in GH responsiveness. Administration of pilocarpine potentiated the GH response to GHRH during the entire life-span of the rats, the only exception being 10-day-old rats in which the drug was without effect. Pilocarpine, though effective in potentiating the GH response to GHRH, did not restore, in senescent rats, GH stimulation to the level of that present in young (3-month old) or adult rats (8-month old). However, the drug was effective in rejuvenating the GH response to GHRH of the older rats (29- and 18-month old) to the level of 15-month-old rats. The present results indicate that modulation of the GH response to GHRH by pilocarpine is consonant with the known changes in the activity of hypothalamic SRIF. Cholinergic drugs may therefore represent a valuable tool to assess SRIF function in physiologic or pathologic conditions of GH secretion, and, in addition, to potentiate GH release during a course of GHRH therapy.

Aging↗

PubMed1990

Generation and amplification of the cytosolic calcium signal during secretory responses to gonadotropin-releasing hormone.

Gonadotropin-releasing hormone (GnRH) stimulates characteristic biphasic increases in cytosolic calcium concentration ([Ca2+]i) and in luteinizing hormone (LH) release in cultured gonadotrophs, with an early peak followed by a prolonged plateau in both responses. Analysis of [Ca2+]i by dual-wavelength fluorimetric assay and of LH release at 5-sec intervals in perifused pituitary cells revealed increases in both responses within a few seconds of exposure to GnRH. The maximum elevation of [Ca2+]i occurred within 20 sec, and the peak gonadotropin release in 35 sec; the total duration of the spike phase for both [Ca2+]i and LH release was 2.5 min. Under extracellular Ca2(+)-deficient conditions, the GnRH-induced peak in [Ca2+]i was reduced by about 20% and the plateau phase was abolished. Concomitantly, the magnitude of the acute phase of LH release was reduced by 40% and that of the second phase by about 90%. Recovery of the plateau phase of LH release occurred within 25 sec after addition of 1.25 mM Ca2+ to Ca2(+)-deficient medium. In a dose-dependent manner, the non-selective Ca2+ channel blockers Co2+ and Cd2+ reduced the Ca2+ current measured by whole-cell recording in pituitary gonadotrophs and abolished the extracellular Ca2(+)-dependent component of LH release. The selective calcium channel blocker, nifedipine, decreased the magnitude of the Ca2+ current and reduced the plateau phase of LH release by 50%; conversely, the dihydropyridine agonist methyl, 1,4,dihydro-2,6-dimethyl 3-nitro-4-(2-trifluorome) (Bay K 8644) consistently enhanced the amplitudes of both Ca2+ current and GnRH-induced LH release. These data reveal a close temporal correlation between changes in [Ca2+]i and LH release during GnRH action, with Ca2+ mobilization during the spike phase and Ca2+ influx through dihydropyridine-sensitive and insensitive sets of receptor-operated calcium channels during the spike and plateau phases. In addition, analysis of the magnitudes of the [Ca2+]i and LH responses to a wide range of GnRH concentrations in the presence and absence of extracellular Ca2+ is consistent with amplification of the [Ca2+]i signal in agonist-stimulated gonadotrops.

Animals↗

PubMed1988

Involvement of the somatostatin and cholinergic systems in the mechanism of growth hormone autofeedback regulation in the rat.

The involvement of the cholinergic system in GH secretion has recently acquired increasing importance. Data have been presented suggesting that in rats the effect of cholinergic modulation on GH secretion takes place through inhibition or stimulation of hypothalamic somatostatin (SRIF) release. To investigate further the significance of cholinergic-SRIF link and its role in the regulation of GH secretion, the action of cholinergic agonist and antagonist drugs in the GH short-loop feedback mechanism mediated by SRIF was investigated. Intracerebroventricular (i.c.v.) infusion of 0.2 or 2.0 micrograms GH/rat into the lateral brain ventricle of adult male rats induced a significant reduction in the GH-releasing hormone (GHRH; 2 micrograms/kg, i.v.)-induced peak GH rise, but only the 2.0 micrograms dose reduced also the GH-integrated area after administration of GHRH. This effect was absent after central administration of 20.0 micrograms GH/rat, due probably to leakage of some GH from the cerebral ventricle into the systemic circulation. Pretreatment with cysteamine (300 mg/kg, s.c.), a known depletor of hypothalamic SRIF, or with anti-SRIF serum (0.5 ml/rat) completely counteracted the lessening of the GH response to GHRH induced by 2.0 micrograms GH injected i.c.v. Similarly, pretreatment with the cholinergic agonist pilocarpine (3 mg/kg, i.v.) completely antagonized the inhibitory effect of central infusion of GH on the GHRH-induced GH response. Atropine (1.0 mg/kg, i.v.), a muscarinic cholinergic antagonist, strikingly inhibited the GHRH-induced GH rise, but when given in combination with i.c.v. infusion of GH there was no additive inhibitory effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Cholinergic agonist and antagonist drugs modulate the growth hormone response to growth hormone-releasing hormone in the rat: evidence for mediation by somatostatin.

Recently, data have been presented showing that muscarinic cholinergic agonists or antagonists can modulate, in opposite ways, GH-releasing hormone GHRH)-induced GH release in man. The aim of the present study was, first, to confirm these findings in the rat and, secondly, if confirmed, to investigate the mechanism(s) subserving the effect of cholinergic drugs. In adult male rats bearing chronic indwelling atrial cannulae, pretreatment with the cholinergic antagonists pirenzepine (0.5 mg/kg, i.v.) or atropine (0.5 mg/kg, i.v.) significantly reduced the rise in plasma GH induced by GHRH (2 micrograms/kg, i.v.), while pretreatment with the cholinergic agonist pilocarpine (3 mg/kg, i.v.) potentiated it. In rats with hypothalamic somatostatin (SRIF) depletion, i.e. rats with anterolateral deafferentation of the mediobasal hypothalamus or rats treated with cysteamine, the modulatory action of cholinergic drugs on the neuroendocrine effect of GHRH was completely lacking. In these two experimental models, an antiserum raised against SRIF failed to elicit a rise in plasma GH and measurement of hypothalamic SRIF content revealed a clear-cut reduction of the neuropeptide. Atropine (1 mumol/l) and pilocarpine (1 mumol/l), added to pituitary cells in vitro, failed to alter GHRH-induced GH release. The present results indicate that muscarinic cholinergic agonists and antagonists modulate GHRH-induced GH release in the rat and suggest that the effect of cholinergic modulation takes place through SRIF.

Afferent Pathways↗

PubMedDate not supplied

Age-related histopathological changes of the stria vascularis: an experimental model.

The stria vascularis (SV) of 3-, 8- and 18-month-old C57 mice was examined with a fluorescence microscope in order to evaluate the capillary density and vessel diameter. The capillary density was significantly reduced in 18-month-old mice compared to 3-month-old (P<0.001) and to 8-month-old (P<0.001) mice. The difference between 3- and 18-month-old mice was significant for the basal, middle and apical cochlear turns, while the difference between 8- and 18-month-old mice was significant only for the middle and basal turns. Vessel diameter within the whole SV was significantly reduced in all turns in 18-month-old mice (P<0.01) versus 3-month-old animals, while vessel diameter was reduced only in the basal turn in 8-month-old versus 3-month-old mice. The results suggest that previously described histopathological changes in the organ of Corti of C57 mice may be related to modifications of strial capillaries.

Age Factors↗