Biomedical subjects

N Burrello

Publications and source records attributed to N Burrello.

24 records · Page 2Linked to original sources

PubMed1996

The kappa-opioid receptor agonist MR-2034 stimulates the rat hypothalamic-pituitary-adrenal axis: studies in vivo and in vitro.

There is increasing evidence that opiates not only have analgesic properties, but also regulate mechanisms activated during the stress response, such as the hypothalamic-pituitary-adrenal (HPA) axis. Indeed, opioid-containing neurons innervate the paraventricular nucleus and the median eminence, thus modulating inputs to ACTH-controlling neurons. In addition, dynorphin (the endogenous ligand of the kappa-opioid receptor)-like peptides have been found co-localized with corticotrophin-releasing hormone (CRH) and are believed to be co-secreted with it in the hypophyseal portal circulation to modulate ACTH release. In this study, we evaluated the effects of the selective kappa-opioid receptor agonist MR-2034 [(-)-N-(2-tetrahydrofurfuryl)-normetazocine] on the HPA axis in vivo and in vitro. MR-2034 was given intravenously to catheterized, freely moving, male Sprague-Dawley rats and serial blood samples were collected for ACTH and corticosterone (B) measurements. We evaluated also the site of MR-2034 action on the HPA axis in vivo, after the administration of alpha-helical CRH9-41, a CRH receptor antagonist, on hypothalamic CRH, pituitary ACTH, and B release in vitro. MR-2034 increased plasma ACTH and B levels in a dose-related fashion and this effect was antagonized by the selective kappa-opioid receptor antagonist MR-1452. In the presence of alpha-helical CRH9-41, the responses of plasma ACTH and B to MR-2034 were blunted significantly, suggesting that this compound activates the HPA axis through a CRH-dependent mechanism. Accordingly, MR-2034 stimulated hypothalamic CRH release in vitro in a concentration-dependent fashion and this effect was antagonized dose-dependently by MR-1452. However, the stimulatory effect of MR-2034 on plasma ACTH and B in vivo was not completely abolished by alpha-helical CRH9-41, suggesting that an additional, CRH-independent, mechanism was involved. Indeed, MR-2034 was able to stimulate basal ACTH output in a dose-dependent manner and this effect was antagonized by MR-1452 in vitro. On the other hand, MR-2034 did not have any effect on B release from adrenocortical cells or adrenal quarters in vitro. These results show that the benzomorphan MR-2034 stimulates the HPA axis in the rat by acting at the hypothalamic and the pituitary level. We hypothesize that endogenous kappa-opioid peptides not only act at the pituitary level to increase ACTH output, but may also act at the hypothalamic level to increase CRH release through an autocrine and/or ultrashort positive feedback mechanism.

Adrenocorticotropic Hormone↗

PubMed1995

Role for serotonin3 receptors in the control of adrenocorticotropic hormone release from rat pituitary cell cultures.

Although several serotonin (5-HT) receptor types have been shown capable of stimulating the release of adrenocorticotropic hormone (ACTH) from the pituitary gland, relatively little is known about the role of the 5-HT3 receptor, a receptor that has generated a great deal of interest for its involvement in many behavioral and therapeutic effects. Hence, in this study, we tested the effects of the 5-HT3/4 receptor antagonist 3-tropanyl-indole-3-carboxylate (ICS 205-930) and the selective 5-HT3 receptor antagonist 3-tropanyl-3, 5-dichlorobenzoate (MDL 72222) on ACTH release stimulated by 5-HT from primary cultures of rat pituitary cells. Subsequently, we evaluated the effects of the selective 5-HT3 receptor agonist 1-(m-chlorophenyl)-biguanide (m-CPBG) on basal, corticotropin-releasing hormone (CRH)- and arginine vasopressin (AVP)-stimulated ACTH release. The maximal stimulatory effect of 5-HT (10(-9) mol/l) on ACTH release was antagonized by both ICS 205-930 and MDL 72222, suggesting that 5-HT stimulates basal ACTH release through activation of 5-HT3, receptors. Accordingly, m-CPBG stimulated basal ACTH release in a concentration-dependent fashion. In contrast to 5-HT, m-CPBG did not have any effect on CRH-stimulated ACTH release and inhibited AVP-stimulated ACTH release in a concentration-dependent manner. These data suggest that the 5-HT3 receptor is involved in the release of ACTH from the pituitary gland in vitro.

Adrenocorticotropic Hormone↗

PubMed1994

Involvement of corticotropin-releasing hormone and endogenous opioid peptides in prolactin-suppressed gonadotropin-releasing hormone release in vitro.

Corticotropin-releasing hormone (CRH) has been shown capable of inhibiting hypothalamic gonadotropin-releasing hormone (GnRH) release through activation of an endogenous opioid peptide (EOP)-dependent mechanism. Recently, we have shown that prolactin (PRL) stimulates CRH release and inhibits GnRH release by hypothalami explanted from male rats. Thus, the present study was undertaken to investigate whether the inhibitory effect of PRL on GnRH release in vitro is mediated by CRH and/or EOP. To this aim, the release of GnRH in response to PRL was evaluated in presence of CRH9-41 alpha-helical (CRH-9-41), a CRH receptor antagonist, and/or naloxone (NAL), a nonselective opioid receptor antagonist, using a static hypothalamic organ culture system which enabled us to evaluate immunoreactive GnRH (iGnRH) release from individually incubated longitudinally halved hypothalamic. As previously shown, PRL at the concentration of 100 nmol/l inhibited basal iGnRH release by about 35%. CRH9-41 or NAL overcame the inhibitory effect of PRL on iGnRH release in a concentration-dependent fashion. The simultaneous co-incubation with both antagonists was not more effective than each single antagonist. CRH9-41 did not have any effect on basal iGnRH release whereas NAL, as previously reported, increased it. In addition, PRL at the concentration of 100 nmol/l stimulated basal hypothalamic beta-endorphin (beta-EP) release. In conclusion, these data show that antagonism to CRH receptors counteracts the suppressive effects of PRL upon GnRH release and that PRL is able to stimulate hypothalamic beta-EP release in vitro.

Animals↗

PubMed1994

Effects of endothelin-1 and endothelin-3 on rat hypothalamic corticotrophin-releasing hormone and pituitary ACTH release in vitro.

Endothelins (ETs) are potent vasoconstrictor peptides that also participate in the regulation of endocrine function. Indeed, immunoreactive ET, ET mRNA and ET receptors have been found in the brain and the pituitary gland and ETs stimulate arginine vasopressin, LH, FSH, TSH and gonadotrophin-releasing hormone and inhibit prolactin release in vitro. The present study was undertaken to evaluate the effects of ET-1 and ET-3, two members of this family, on corticotrophin-releasing hormone (CRH) release by explanted male rat hypothalami in vitro and on ACTH release by primary pituitary cell culture. ET-3 decreased basal CRH release in a concentration-related manner. The lowest effective concentration tested was 3 nmol/l but a more pronounced inhibitory effect was obtained at a concentration of 10 nmol/l. On the other hand, ET-1 did not have any detectable effect on basal CRH release. Neither ET-1 nor ET-3 had any effect on the release of CRH stimulated by potassium chloride. ET-1 increased basal ACTH release, whereas ET-3 did not have any effect. Both ET-1 and ET-3 suppressed the release of ACTH stimulated by 1 nmol CRH/l. These data suggest that both ET-1 and ET-3 are able to modulate the hypothalamic-pituitary-adrenal axis function in vitro. However, they act at different levels and seem to have opposite effects. Indeed, while ET-1 stimulated pituitary ACTH release, ET-3, the peptide produced mainly in the brain, inhibited hypothalamic CRH release in vitro.

Adrenocorticotropic Hormone↗

PubMedDate not supplied

Sperm aneuploidy in infertile men.

A recent line of research has shown that infertile male patients produce cytogenetically abnormal spermatozoa, despite a normal somatic karyotype, as a result of an altered intra-testicular environment that affects negatively the mechanisms controlling chromosome segregation during cell division. The rate of aneuploid spermatozoa production is significantly higher in patients with abnormal sperm parameters compared with those of normozoospermic subjects or infertile patients with normal sperm parameters. All chromosomes are subject to aneuploidy, although at a different rate; the heterochromosomes are more often altered than are the autosomes. A negative correlation has been reported to exist between aneuploidy and the main sperm parameters, suggesting that greater testicular damage is associated with a greater chance of chromosome malsegregation events. Abnormally-shaped spermatozoa are more likely to have chromosome abnormalities, particularly those with an enlarged head. More studies are necessary, however, to evaluate whether other types of sperm head abnormalities are also associated with an abnormal sperm chromosome complement. The possibility of retrieving testicular or epididymal spermatozoa in patients with azoospermia and using them in assisted reproduction techniques has prompted the evaluation of their chromosomal status. Studies have shown that testicular and epididymal spermatozoa have a greater rate of aneuploidy compared with that of ejaculated spermatozoa. Some authors have also shown that patients with non-obstructive azoospermia have a significantly higher sperm aneuploidy rate compared with that of patients with obstructive azoospermia. Sperm aneuploidy seems to have a negative impact on assisted reproduction technique outcome. Although it does not affect the fertilization rate, an elevated sperm aneuploidy rate is associated with a greater rate of pregnancy failure. Nevertheless, some patients with elevated sperm aneuploidy rate can still achieve a pregnancy, but with an increased risk of generating an aneuploid offspring. Thus, sperm aneuploidy evaluation is recommended in infertile patients with abnormal semen parameters, particularly if they undergo IVF programmes.

Aneuploidy↗

PubMedDate not supplied

Relationship of inhibin serum level to bioactive and immunoreactive FSH in oligospermic and azoospermic patients.

The purpose of the study described here was to evaluate the relationship between inhibin (INH) and bioactive FSH (B-FSH) or immunoreactive FSH (I-FSH) in oligoazoospermic patients. To accomplish this, the authors measured serum levels of INH, I-FSH, B-FSH, LH and testosterone (T) in 98 male patients attending the andrology Centre at Malphighi Hospital (Bologna) for infertility workup. On the basis of the mean sperm concentration, patients with sperm output > or = 4 x 10(7) ml-1 (n = 30) formed the control group (group A), whereas oligozoospermic patients were divided arbitrarily into three groups. Sperm concentrations for these groups ranged as follows: B, 2-4 x 10(7) ml-1 (n = 14); C, 5 x 10(6)-2 x 10(7) ml-1 (n = 18); D, < 5 x 10(6) ml-1 (n = 17). In addition, the authors studied a group of patients with possible non-obstructive azoospermia (n = 19, group E), confirmed in 16 of them through testicular biopsy. There were no significant differences in serum levels of LH and T among groups. However, azoospermic patients had a significant reduction of the T/LH ratio. Similarly, B-FSH and B/I-FSH ratios were significantly elevated only in group E. INH serum levels did not show any appreciable changes among groups and in azoospermic patients INH correlated significantly and in a positive manner with I-FSH serum levels and negatively with B/I-FSH and T/LH ratios. Within the azoospermic patient group no consistent relationship was evident between INH serum concentration and various degrees of spermatogenetic arrest.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗