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Adrenomedullin stimulates proliferation and inhibits apoptosis of immature rat thymocytes cultured in vitro
No full textAdrenomedullin (AM) is a hypotensive peptide, which derives from the proteolytic cleavage of pro(p)AM, and acts through two subtypes of receptors, named L1-receptor (L1-R) and calcitonin receptor-like receptor (CRLR). CRLR functions as either a calcitonin gene-related peptide (CGRP) receptor or a selective AM receptor depending on which member of a family of receptor-activity-modifying proteins (RAMPs) is expressed: RAMP1 generates CGRP receptors, while RAMP2 and RAMP3 produce AM receptors. Reverse transcription (RT)-polymerase chain reaction (PCR) consistently allowed the detection of pAM and peptidyl-glycine alpha-amidating monooxygenase (the enzyme converting immature AM to the mature peptide) mRNAs in the thymus cortex of immature (10-day-old) rats. Accordingly, radioimmune assay (RIA) measured low but sizeable AM concentrations in this tissue. RT-PCR also demonstrated the presence of the specific mRNAs of L1-R, CRLR and RAMPs. AM (from 10(-9) to 10(-7)M) increased proliferation index and lowered apoptotic index of cultured immature rat thymocytes, and the effects were annulled by the AM receptor antagonist AM(22-52). In conclusion, our study demonstrated that (1) immature rat thymus cortex expresses AM and the AM receptors L1-R and CRLR/RAMP; and (2) AM, acting via AM(22-52)-sensitive receptors, exerts a potent growth promoting effect on immature rat thymus, by enhancing proliferation and lowering apoptotic death of thymocytes. Taken together, these findings could suggest that AM may play a role in the development of immunity
Effect of cerebellin on the pituitary-adrenocortical function in adult rats and the proliferative activity of immature and regenerating rat adrenal cortex
No full textInvestigation of the effect of different regulatory peptides on adrenocortical cell proliferation in immature rats: Evidence that endogenous adrenomedullin exerts a stimulating action
No full textCompelling evidence indicates that the active growth of immature rat adrenal glands is sustained not only by an increased release of pituitary ACTH, but also by other ancillary mechanisms. We investigated whether vasoactive intestinal peptide (VIP), atrial natriuretic peptide (ANP), adrenomedullin (ADM) and proadrenomedullin N-terminal 20 peptide (PAMP) play a relevant role in these mechanisms. These four regulatory peptides were chosen because previous studies demonstrated that they are expressed in rat adrenals and are able to modulate the secretory activity and growth of zona glomerulosa (ZG), i.e., the adrenal layer. Groups of immature (20-day old) rats were given three subcutaneous injections (28, 16 and 4 h before sacrifice) of 2 nmol/100 g of the four peptides and/or selective antagonists of their receptors (VIP-A, ANP-A, ADM-A and PAMP-A), and 0.1 mg/100 g vincristin 3 h before autopsy. Adrenal glands were collected, processed for light microscopy, and the mitotic index (MI; percentage of metaphase-arrested cells) was evaluated in the subcapsular ZG. Neither VIP nor VIP-A affected MI. Both ANP and ANP-A decreased MI and their effects displayed additivity. ADM and PAMP raised MI and the effect was abolished by ADM-A and PAMP-A, respectively. When administered alone ADM-A, but not PAMP-A, significantly lowered MI. Collectively, our findings suggest that: i) neither VIP nor PAMP are involved in the regulation of immature rat adrenals; ii) ANP exerts a non-receptor-mediated inhibitory action, whose physiological relevance remains to be investigated; and iii) endogenous ADM system plays a relevant role in the mechanisms underlying the maintenance of high growth rate during adrenal maturation
Neuromedin-U inhibits unilateral adrenalectomy-induced compensatory adrenal growth in the rat
No full textNeuromedin-U (NMU) is a brain–gut peptide, which has been previously found to stimulate
hypothalamic–pituitary–adrenal axis in the rat and to control the growth of the rat adrenal cortex.
The present study aimed to investigate the possible involvement of NMU in the regulation of unilateral
adrenalectomy-induced compensatory adrenal growth, a phenomenon known to be neurally mediated.
The right adrenal gland ofmature female rats was removed, the contralateral gland was then analyzed at
24 and 72 h following surgery. Groups of rats were given 3 subcutaneous injections (24, 16 and 8 h before
decapitation) ofNMU8 (1.5 or 3.0 nmol/100 g/per injection). Three hours before sacrifice all rats received
an intraperitoneal injection of 0.1 mg/100 g body weight of vincristin. By means of RT-PCR the presence
of NMUR1 mRNA was detected in adrenal cortex of both intact and hemiadrenalectomized rats. As
expected, unilateral adrenalectomy-induced an increase in adrenal weight, associated with increased
plasma ACTH, aldosterone and corticosterone levels. The administration of NMU to hemiadrenalectomized
rats did not significantly affect these parameters. NMU administration, however, notably
inhibited the unilateral adrenalectomy-induced adrenocortical cell proliferation in both zona
glomerulosa and zona fasciculata, as assessed by the metaphase index and the number of parenchymal
cell nuclei per unit area of the tissue. When compared to hemiadrenalectomized animals receiving
saline, a significant decrease of blood corticosterone levels was observed after 24 h in rats treated with
the highest dose of NMU. Since these effects were independent on changes in blood ACTH, they could
reflect an interaction of NMU with the neural system innervating the adrenal gland
Effects of orexins A and B on the secretory and proliferative activity of immature and regenerating rat adrenal glands
No full textOrexins A and B are two hypothalamic peptides, involved in the central regulation of feeding, which act through two receptor subtypes, named OX1R and OX2R. OX1R is selective for orexin-A, and OX2R binds both orexins. We have investigated the effects of three subcutaneous injections of 10 nmol/kg body weight of orexins on the secretion and proliferative activity of immature (20-day-old) and regenerating rat adrenal cortex. The presence of both OX1R and OX2R mRNAs has been detected by reverse transcription-polymerase chain reaction in adult, immature and regenerating adrenals. Orexin-A increased corticosterone plasma concentration in immature rats, but not in animals with regenerating adrenals. Both orexins raised metaphase index (%o of metaphase-arrested cells) in immature rat adrenals, orexin-B being more effective than orexin-A. In contrast, both orexins equipotently lowered adrenal metaphase index at day 5 (but not day 8) of adrenal regeneration. We conclude that orexins (1) stimulate secretion and proliferative activity of immature rat adrenals, acting through OX1R and OX2R, respectively; and (2) do not affect secretion, but inhibit proliferative activity of regenerating adrenals, mainly via the activation of OX2R
Effects of galanin on the proliferative activity of immature rat adrenal gland, as investigated by metaphase-arrest and PCNA-immunostaining techniques
No full textEndogenous cholecystokinin (CCK) exerts a tonic inhibitory action on rat pituitary-adrenocortical axis, acting through the CCK-B receptor subtype
No full textExendin-4, a GLP-1 receptor agonist, stimulates pituitary-adrenocortical axis in the rat: Investigations into the mechanism(s) underlying Ex4 effect
No full textExendin-4 (Ex4) is a potent and long-lasting agonist of glucagon-like peptide-1 (GLP-1), which has been previously found to stimulate pituitary-adrenal axis in the rat. Aim of the present study was to gain insight into the mechanism(s) involved in the Ex4-induced rise in the rat plasma concentrations of ACTH, aldosterone and corticosterone. Preliminary time- and dose-response studies showed that the maximum stimulating effect of Ex4 occurred within 1 or 2 h and at dose ranging from 0.5 to 2.0 nmol/100 g body weight. The GLP-1 receptor (GLP-1R) antagonist Ex(9-39) did not significantly affect ACTH, aldosterone and cortico-sterone responses to Ex4. Neither the administration of CRH and arginine vasopressin (AVP)-receptor antagonists nor adrenal demedullation prevented pituitary-adrenal axis responses to Ex4. The prolonged (4 or 6 days) suppression of the pituitary ACTH release by dexamethasone impaired corticosterone, but not aldosterone response to Ex4. The following conclusions are drawn: i) Ex4 stimulates rat pituitary-adrenal axis through receptors other than the classic GLP-1R; ii) neither CRH and AVP nor medullary catecholamines are involved in the Ex4-induced stimulation of ACTH release; iii) ACTH stimulation accounts for the rise in corticosterone plasma concentration; and iv) the aldosterone secretagogue effect of Ex4 occurs via a mechanism independent of the stimulation of either ACTH or medullary catecholamines
Effects of endogenous galanin on the growth of regenerating rat adrenal gland as investigated by the metaphase-arrest and the PCNA-immunostaining techniques
No full textWe have investigated the effects of three subcutaneous injections of 2 nmol/100 g body weight of galanin and its receptor antagonist (galanin-A) [D-Thr 6,D-Trp 8,9,-15-ol]-galanin 1-15 on the proliferative activity of regenerating rat adrenal cortex. The metaphase-arrest and the proliferating-cell nuclear antigen (PCNA)-immunostaining techniques were used to estimate the number of M phase (metaphase index) and S phase cells (PCNA index), respectively. Galanin-A raised the metaphase index at both day 5 and day 8 of regeneration. Galanin was per se ineffective, but reversed the galanin-A effect at day 8. Neither galanin nor galanin-A changed PCNA index at day 5. Galanin evoked a moderate increase in PCNA index at day 8. Taken together, these findings indicate that endogenous galanin exerts a tonic maximal inhibitory effect on adrenal regeneration in the rat
Effect of pentagastrin on steroid secretion and proliferative activity of regenerating rat adrenal cortex
No full textThe effects of three subcutaneous injections of 3 nmol/100 g body weight of the cholecystokinin type 2 (CCK2) receptor agonist pentagastrin on adrenocorticotrophic hormone (ACTH) and corticosterone secretion and proliferative activity of regenerating rat adrenal cortex were investigated. Pentagastrin did not alter either ACTH and corticosterone plasma concentrations or the adrenal mitotic index at day 5 of regeneration. In contrast, it increased (by about 50%) the adrenal mitotic index at day 8 of regeneration, and the effect was blocked by the simultaneous administration of equimolar doses of the CCK2-receptor antagonist PD-135,158. It is suggested that the activation of CCK2 receptors exerts a growth promoting action on the regenerating rat adrenal cortex
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