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Biomedical subjects

E Spinedi

Publications and source records attributed to E Spinedi.

12 recordsLinked to original sources
PubMed1992

Cytokines stimulate the CRH but not the vasopressin neuronal system: evidence for a median eminence site of interleukin-6 action.

Antigen-activated immune cells acutely release cytokines which, besides their effects on the immune system, increase hypothalamopituitary-adrenocortical (HPA) function to counteract the inflammatory process. The present study was designed to test, using in vitro paradigms, whether there exists a hypothalamic and/or a median eminence site of action, whereby different substances derived from the immune system could stimulate the CRH and/or the arginine-vasopressin (AVP) neuronal pathway. For this purpose, whole medial basal hypothalamus (containing the median eminence) were dissected from female rats and incubated in vitro with several concentrations of interleukin-1 (IL-1)beta, interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, thymosin fraction 5 (TF5) or bacterial lipopolysaccharide (LPS). After a 40-min incubation period, the amounts of CRH and AVP released into the incubation medium were measured by specific radioimmunoassays (RIAs). Additional experiments were carried out by superfusing isolated rat median eminence fragments with the different test substances; CRH and AVP released into the medium were also measured by RIAs. The results indicated that IL-1 beta (10(-11) to 10(-7) M), IL-6 (0.06 x 10(-10) to 0.4 x 10(-10) M), TNF-alpha (6 x 10(-9) to 6 x 10(-7) M) and TF5 (5-500 micrograms/ml) but not LPS (1-100 ng/ml) significantly enhanced hypothalamic CRH secretion above baseline in a concentration-related fashion. Additionally, superfusion experiments demonstrated that, among all test substances, only IL-6 possesses a direct and dose-dependent CRH-releasing activity at the median eminence level. Conversely, no preparation enhanced basal AVP release in either in vitro design.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1992

Effects of gonadectomy and sex hormone therapy on the endotoxin-stimulated hypothalamo-pituitary-adrenal axis: evidence for a neuroendocrine-immunological sexual dimorphism.

Bacterial lipopolysaccharide (LPS) stimulates the hypothalamo-pituitary-adrenal axis by a mechanism involving the release of cytokines, which activate the CRH-ACTH system and, as a result, increase glucocorticoid secretion. In the present study we investigated the possibility that endogenous sex hormones modulate the in vivo endotoxin-stimulated adrenal and immune responses in adult BALB/c mice. In preliminary experiments we determined that the maximal glucocorticoid release in response to LPS (50 micrograms, ip) administration was reached 2 h after treatment. The endotoxin effect on the adrenal and immune responses was then tested in male, randomly cycling female, 20-day-gonadectomized and 20-day-gonadectomized mice treated with either testosterone or estradiol. In addition, in vitro experiments were performed to determine whether 1) LPS exerts any direct effect on basal and ACTH-stimulated corticosterone release, and 2) adrenal function is influenced by bilateral gonadectomy and sex steroid therapy. Our results indicate that 1) randomly cycling female mice have significantly more pronounced corticosterone secretion than males 2 h after endotoxin injection, although the tumor necrosis factor responses were similar; 2) the response of the hypothalamo-pituitary-adrenal axis to endotoxin stimulation in female mice was invariable throughout the different stages of the normal estrous cycle; 3) gonadectomy leads to enhanced (P < 0.05) adrenal and immune responses to LPS stimulation compared to the responses in shams; 4) the endotoxin-elicited adrenal and immune overresponses observed in gonadectomized mice are reversed by testosterone treatment, regardless of sex; 5) LPS does not directly modify spontaneous and ACTH-stimulated adrenal corticosterone secretion; and 6) gonadectomy alone or combined with sex steroid therapy does not increase the in vitro adrenal response to ACTH stimulation. Our findings further suggest an evident neuroendocrine-immunological sexual dimorphism during the acute phase of inflammatory processes.

Adrenocorticotropic Hormone↗
PubMed1991

Changes in the hypothalamo-corticotrope axis after bilateral adrenalectomy: evidence for a median eminence site of glucocorticoid action.

Bilateral adrenalectomy (ADX) leads to increased ACTH synthesis and secretion. It is thought that endogenous glucocorticoids exert a feedback mechanism at both pituitary and brain levels. The present study has been performed in order to determine the effect of ADX on the release of hypothalamic neuropeptides with corticotropin-releasing activity (CRA) and if there exists a median eminence site of glucocorticoid action to regulate hypothalamic-pituitary-adrenal (HPA) function. Adrenalectomized and sham-operated male rats were killed at different periods after surgery (2, 5, 7 and 14 days) and trunk blood was collected for ACTH and corticosterone (B) concentrations measurement. Brain (median eminence, ME; and medial basal hypothalamus, MBH) and pituitary (anterior lobe, AP; and neurointermediate lobe, NIL) tissues were dissected in order to evaluate either peptide content or in vitro hormone release. The results indicate that ADX blunted plasma B levels and increased AP ACTH content and secretion in a time-related fashion up to the 14th day. ADX significantly decreased both CRF and CRA contents in the ME at all periods studied; ME arginine-vasopressin (AVP) increased 7 and 14 days after ADX. MBH CRF decreased after ADX, but returned to sham value 2 weeks later; similarly, MBH AVP decreased at all periods after ADX. Removal of endogenous glucocorticoids did not vary neither oxytocin (OXY) content in the ME and MBH nor AVP and OXY contents in the NIL. In our superfusion experiments, we found that ADX increased basal AVP release and did not change spontaneous CRF secretion from ME terminals. Dexamethasone (Dxm, 10 nM) diminished AVP but not CRF output by ME tissues from adrenalectomized rats. A direct relationship was found between ME CRF and 28 mM KCl (hK+)-induced CRF release by MEs from adrenalectomized rats. ME fragments from adrenalectomized rats were hyperresponsive to kH+ stimulation of AVP release. Dxm (10 nM) decreased the hK(+)-evoked CRF and AVP release by MEs from adrenalectomized rats. ADX and dexamethasone treatment did not influence basal and hK(+)-elicited ME OXY release. Additionally, a rapid glucocorticoid inhibitory effect on ACTH secretion by isolated AP cells from both sham and adrenalectomized rats was found, and an in vitro corticotrope hyporesponse to 0.63 nM CRF and 9.25 nM AVP stimulation during several days after ADX.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenalectomy↗
PubMed1991

Anterograde nerve degeneration after superior cervical ganglionectomy coexists with a decrease in arginine vasopressin release in rats.

After bilateral superior cervical ganglionectomy (SCGx) in adult male rats, norepinephrine content of the pituitary neurointermediate lobe (NIL) decreased at 12-24 h after surgery to attain concentrations 40-60% of controls between 24 and 60 h after surgery. To assess arginine vasopressin (AVP) secretion during this time, plasma and NIL-AVP levels were measured by radioimmunoassay. In sham SCGx controls, plasma AVP increased about 2-fold within 6 h after surgery and decreased thereafter, to attain presurgical values by 60 h after surgery. In SCGx rats, a significant increase in plasma AVP concentration was observed at the 6th h after surgery, as compared to presurgical concentrations, with a decrease to values significantly lower than those of presurgical controls at 16-18 h after SCGx. As compared to sham-operated rats, significantly higher plasma AVP levels 6 h after surgery and significantly lower plasma AVP levels 16-24 h after surgery were found. NIL-AVP concentration in SCGx and sham-operated ras were significantly lower than presurgical levels at 6 h after surgery. SCGx rats had significantly higher amounts of AVP in NIL at 16-24 h after surgery. The changes in plasma and NIL-AVP levels found 6 or 16 h after SCGx or sham SCGx were unaffected by a prior pinealectomy. Two injections of the alpha 1-adrenoceptor blocker prazosin 45 and 90 min before sacrifice, alone or together with the beta-blocker propranolol, prevented the increase in plasma AVP found in SCGx rats 6 h after surgery, and the decrease in plasma AVP and the increase of NIL-AVP found 16 h after SCGx.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Analysis of the hypothalamic-pituitary-ovary axis in the neonatally-androgenized female rat.

The administration of testosterone propionate (TP) in the female rat at the neonatal age has been used for several yr as a model to study anovulation during adulthood. The present work was designed in order to see whether some neuroendocrine parameters vary with age in this animal model. Hypothalamic LHRH content and LH-FSH anterior pituitary (AP) content and plasma levels were evaluated in samples taken from both neonatally-androgenized and littermate control female rats at different ages (15 to 100 days old). Additionally, we have studied pulsatile LH-FSH released in plasma and in vivo AP response to LHRH in both neonatally-androgenized and control female rats during adulthood. The results indicate that the neonatal TP treatment did not induce any change in hypothalamic LHRH content over development. Neonatally androgenized rats have decreased both LH-FSH AP content and plasma levels at the infantile age (15-day old). LH-FSH AP content remained reduced in samples taken up to the 30th day of age. Plasma LH-FSH levels on the day 30 of age were similar in both groups. TP-treated rats studied on the 100th day of age had: a) an altered pulsatile rhythm of gonadotropin release in plasma due to the decreased LH-FSH trough and average mean values, and to the diminished FSH peak amplitude values, as well as an increased LH:FSH ratio; and b) an impaired in vivo LHRH-induced LH-FSH release.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1990

Increase in adrenocorticotropin release during wallerian degeneration of peripheral sympathetic neurons after superior cervical ganglionectomy of rats.

The changes in adrenocorticotropin (ACTH) release before, during and after sympathetic nerve degeneration following superior cervical ganglionectomy (SCGx) were examined in male rats. A 12-fold increase of circulating ACTH was found in both SCGx and sham-operated rats 6 h after surgery. In sham-operated rats, plasma ACTH decreased by about half 16-22 h after surgery, whereas in SCGx rats it remained at a high concentration from 16 to 54 h after surgery, attaining basal values by 120 h post-SCGx. In SCGx rats, MBH corticotropin-releasing hormone (CRH) content decreased significantly from 16 to 54 h after surgery, while in controls it remained unmodified. Significantly smaller arginine vasopressin (AVP) contents were found in MBH of SCGx rats as compared to sham-operated controls, 16-54 h after surgery. In rats exposed to ether or immobilization stress 22 h after SCGx, plasma ACTH levels were significantly higher than in controls; however, since unstressed ACTH levels were about twice as high in SCGx rats, the percent increase of ACTH was smaller in the SCGx group. A decreased response of plasma ACTH to ether or immobilization stress was found in rats 7 days after SCGx. In rats subjected to a simultaneous adrenalectomy (Adx) and SCGx or sham-SCGx, plasma ACTH levels increased to a similar extent in both groups. ACTH increase after Adx was accompanied by decreases in MBH CRH, and absence of significant changes in MBH AVP contents. Rats subjected to pinealectomy (Px) or sham-Px 1 week earlier and killed 22 h earlier exhibited similar responses in plasma ACTH and MBH CRH to SCGx regardless of pineal intactness.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1989

Angiotensin II and glucocorticoid release: direct effect at the adrenal level and modulation of the adrenocorticotropin-induced glucocorticoid release.

Angiotensin II (A II) stimulates adrenal glomerulosa cells releasing mineralocorticoids; however, little is known about the A II effect on glucocorticoids output. The present study has been designed in order to see if A II could modify in vitro spontaneous and ACTH-induced corticosterone (B) release from both fasciculata-reticularis enriched and total adrenal cells. The results indicate that A II at 10(-12), 10(-11), 10(-10) and 10(-6) M concentrations did not modify basal B production and A II 10(-9), 10(-8) and 10(-7) M decreased basal B production from total adrenal cells. Whereas A II (10(-10)-10(-6) M) stimulated B release from fasciculata-reticularis enriched cells. On the one hand, 10(-8) M A II significantly decreased ACTH-elicited B release from total adrenal cells; effect completely abolished by saralasin (SAR, 10(-8) M), a specific A II receptor blocker. On the other hand, 10(-8) M A II did not modify ACTH-induced B release from fasciculata-reticularis enriched cells. Finally, 10(-10) to 10(-6) M A II and 22 pM ACTH stimulated aldosterone output from total adrenal cells; while, fasciculata-reticularis enriched cells did not secrete any measurable amount of aldosterone under basal condition and after incubation with A II. These data further suggest a regulatory role of A II in the release of glucocorticoids from the adrenal gland.

Adrenal Glands↗
PubMed1988

Role of central epinephrine on the regulation of corticotropin-releasing factor and adrenocorticotropin secretion.

Epinephrine (EPI) has been described to stimulate the hypothalamic-pituitary-adrenal axis. However, whether central EPI neuronal systems play a major physiological role in the regulation of ACTH secretion and whether that role is primarily stimulatory or inhibitory in nature is still controversial. The present study addressed these questions using different inhibitors of phenylethanolamine-N-methyltransferase (PNMT), which were either active peripherally or were both peripherally and centrally active. Male rats received either vehicle or a PNMT inhibitor at various times before further experimental procedures. A large decrease in hypothalamic EPI levels was observed in rats given central PNMT inhibitors, whereas these treatments did not affect hypothalamic norepinephrine (NE) levels. Plasma EPI, but not NE, was decreased to similar levels after treatment with peripheral or central PNMT inhibitors. Basal plasma ACTH decreased slightly during the 12 h after central PNMT inhibition. Central, but not peripheral, inhibition of PNMT significantly decreased the plasma ACTH response to ether vapor stress at 5 and 15 min. This effect was seen 3 or 12 h after PNMT inhibition. The suppression of the stress response was not due to a change in responsiveness of the pituitary to CRF. The hypothalamic content of CRF was significantly decreased 9 and 12 h after inhibition of central PNMT. Blockade of the stress response actually preceded the changes in CRF levels. The content of arginine vasopressin, another potent ACTH secretagogue, was not affected 3, 6, 9, or 12 h after that treatment. The effect on CRF was not observed in rats treated with the peripheral PNMT inhibitor, nor was it caused by manipulation and stress of the animals 12 h before death. The dat demonstrate that central inhibition of PNMT, which produces a selective decrease in hypothalamic EPI levels, blunts the response of plasma ACTH to ether vapor stress, and at later times also causes a selective decrease in CRF content. Furthermore, the altered ACTH response to ether stress is not due to a change in responsiveness of the pituitary to CRF or to an alteration in arginine vasopressin levels. Thus, an endogenous EPI neuronal system appears to stimulate CRF neurons responsible for the increase in ACTH after ether vapor stress.

Adrenocorticotropic Hormone↗
PubMed1988

Angiotensin II (AII) and adrenocorticotropin release: modulation by estradiol of the AII biological activity and binding characteristics in anterior pituitary dispersed cells.

The present studies were designed to test if estrogens influence basal and angiotensin II (AII)-stimulated ACTH release and the binding characteristics of AII receptors in isolated anterior pituitary (AP) cells from estrogen-deplete and estrogen-replete rats incubated in vitro. AP cells were obtained from various adult donors: randomly cycling (rc), 10-day ovariectomized (Ovx), Ovx with estradiol restored at a circulating physiological level (Ovx + lEB), Ovx with estradiol at a supraphysiological circulating level (Ovx + hEB); and male (m) rats. The amount of ACTH released under basal conditions was similar in the rc, Ovx + lEB, and m groups, although this amount was significantly greater (P less than 0.02) than that in the Ovx and Ovx + hEB groups. The ACTH-releasing activity (CRA) of AII was concentration dependent (10(-9)-10(-6) M) in all cells. The rank order of the CRA of AII in the groups varied as follows: rc = Ovx + lEB greater than Ovx = Ovx + hEB = m. The slopes of the AII responses were similar. Estradiol addition in vitro did not modify either basal or AII-stimulated ACTH release in any group of cells. AII binding studies indicated that AP cells from donors with different circulating estradiol levels had similar apparent equilibrium dissociation constants (Kd, 16-30 nM). However, the maximum binding capacities in AP cells from the m, Ovx, and Ovx + hEB groups (40, 51, and 49 fmol/10(6) cells, respectively) were significantly lower (P less than 0.05) than those in the rc and Ovx + lEB groups (77 and 81 fmol/10(6) cells, respectively). In summary, these studies indicate that 1) circulating levels of estradiol are able to modulate spontaneous ACTH release by dispersed AP cells; and 2) circulating estradiol, at a lower or higher level than that during the estrous cycle, decreases the in vitro ACTH-releasing activity of AII, possibly through a reduction in the number of AP AII receptors. These results further suggest that estrogen is likely to have a physiological role in corticotropic function.

Adrenocorticotropic Hormone↗
PubMed1986

Angiotensin II and adrenocorticotropin release: mediation by endogenous corticotropin-releasing factor.

Recent reports indicate that the main effect of systemically administered angiotensin II (AII) on ACTH release is probably due to some central nervous system mechanism. The present studies were designed to investigate whether the central action of AII on ACTH release is directly mediated through CRF. In order to test the participation of endogenous CRF in the AII-induced ACTH release in vivo, intact and pharmacologically blocked (pretreated with chlorpromazine-morphine-nembutal) female rats were injected iv with AII (8 nmol/100 g BW). Plasma levels of ACTH as well as CRF content in the median eminence (ME) and medial basal hypothalamus (MBH) were evaluated before and 1, 2.5, and 5 min after treatment. These responses were compared with the effect of 1 min ether exposure on hypothalamic CRF content and plasma ACTH levels in unanesthetized animals. AII injection and ether exposure increased plasma ACTH levels several-fold at both 2.5 and 5 min post treatment in intact rats. Conversely, AII failed to induce any significant increase in plasma ACTH levels in centrally blocked rats at any interval studied. On the other hand, AII injection and ether inhalation acted in similar fashion on CRF content in ME, inducing fast depletion at 1 min post treatment, recovering to control values at 2.5 min after injection, and finally, accumulating peptide at 5 min post treatment. In addition, CRF content in the MBH decreased significantly at 5 min, under both experimental conditions; AII had no effect on hypothalamic CRF content in centrally blocked rats. In vitro experiments using whole MBH (containing ME) fragments incubated with either neural peptides or high K+ solutions indicate that AII possesses a CRF releasing effect at concentrations of 10(-6) M or more. Conversely, other hypothalamic peptides, such as LHRH, TRH, and somatostatin did not induce significant release of CRF at any of the concentrations assayed (10(-7) to 10(-5) M). On the other hand, high K+ solutions released CRF in a concentration-related manner (15-60 mM). These studies suggest that the central effect of AII stimulation on ACTH release in vivo could be, at least in part, through the release of hypothalamic CRF into the portal circulation.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Stimulation of the hypothalamo-pituitary-adrenocortical axis by the central serotonergic pathway: involvement of endogenous corticotropin-releasing hormone but not vasopressin.

Many reports indicate that serotonin plays a role in the regulation of the hypothalamo-pituitary-adrenocortical axis. The present study was designed to elucidate whether the activation of the central serotonergic pathway enhances adrenocorticotropin and corticosterone secretion, and if so, whether the CRH and vasopressin neuronal systems could be mediating this effect. Intraperitoneal administration of a low dose of L-5-hydroxytryptophan (an aromatic L-amino acid precursor of serotonin synthesis; 20 mg/kg bw, 30 minutes before the sacrifice) in rats pretreated with pargyline (a brain monoamine oxidase inhibitor, which enhances monoamine activity; 75 mg/Kg bw, 16 hours before the sacrifice) and carbidopa (a peripheral active inhibitor of the decarboxylation of aromatic L-amino acids, which would permit more monoamine precursor to be available to the brain; 50 mg/Kg bw, 90 minutes before the sacrifice) increased ACTH and corticosterone secretion in plasma. Such an effect was partially blocked by metergoline (a serotonin type-1 and-2 receptor blocker; 1 mg/Kg bw, 90 minutes before the sacrifice), but not by spiperone (a serotonin type-2 and dopamine receptor antagonist; 0.5 mg/Kg bw. 90 minutes before the sacrifice). The activation of the central serotonergic system enhanced the CRH content in the median eminence, whereas it decreased the content of this neuropeptide in the medial basal hypothalamus. These effects were fully abolished by metergoline, but not by spiperone pretreatment. The activation of the serotonergic pathway did not influence the vasopressinergic neuronal system. In vitro experiments using hypothalamic-median eminence fragments incubated with serotonin solutions indicate that this monoamine possesses a CRH releasing effect at concentrations of 1 microM or more.(ABSTRACT TRUNCATED AT 250 WORDS)

5-Hydroxytryptophan↗