Biomedical subjects

L K Malendowicz

Publications and source records attributed to L K Malendowicz.

At least 109 records · Page 6Linked to original sources

PubMed1995

Effects of oxytocin on the function and morphology of the rat adrenal cortex: in vitro and in vivo investigations.

The effects of oxytocin (OX) on the function and morphology of the rat adrenal cortex were studied in vivo and in vitro. OX exerted a potent stimulatory action on basal, but not 10(-8) M ACTH-stimulated corticosterone (B) secretion of dispersed rat inner (zona fasciculata and zona reticularis) adrenocortical cells (maximal effective concentration: 10(-9) M); in contrast, at higher concentrations (10(-7)/10(-6) M) OX inhibited maximally ACTH-stimulated B output. A single subcutaneous (s.c.) injection of 1.2 nmol/100 g body weight OX resulted in a long-lasting (up to 12 h) rise in plasma B concentration (PBC). The prolonged administration of OX (daily s.c. injections of 0.6 or 1.2 nmol/100 g for 10 days) caused a marked lowering in the adrenal weight and volume of all adrenocortical zones, that in turn was due to a decrease in the number of their parenchymal cells; however, the average volume of inner adrenocortical cells was significantly increased. Basal PBC was lowered, but its response to ether stress was unchanged in comparison with control rats. Prolonged OX treatment did not change B secretion by adrenal slices, but it markedly raised that of dispersed inner adrenocortical cells. Our present findings clearly show that the effects of OX on the adrenal cortex depend on the experimental model employed (in vitro versus in vivo) and the duration of treatment (acute versus chronic). Taken together they allow us to conclude that OX exerts an acute direct stimulatory effect on the rat adrenal cortex, and a chronic inhibitory one, that at least in part could be due to the interference of OX with the mechanism(s) of intracellular transduction of the ACTH secretagogue signal.

Adrenal Cortex↗

PubMed1995

Effects of pituitary adenylate-cyclase activating peptide (PACAP) on the rat adrenal secretory activity: preliminary in-vitro studies.

PACAP did not affect secretory activity of dispersed rat adrenocortical cells, but it markedly raised aldosterone (ALDO) and corticosterone (B) production by adrenal slices, containing both medullary and cortical tissues. The secretagogue effects of PACAP were suppressed by PACAP(6-38), a specific competitive antagonist. Isoprenaline (IP) enhanced ALDO, but not B secretion of adrenal slices, and l-alprenolol (AL) completely blocked IP effect. AL and corticotropin-inhibiting peptide (CIP) partially reversed ALDO response to a maximal effective concentration of PACAP; AL did not affect B response to a maximal effective concentration of PACAP, while CIP completely annulled it. Quarters of regenerated adrenocortical autotransplants, that are completely deprived of chromaffin cells, though displaying ALDO and B responses to IP and ACTH, were insensitive to PACAP. The hypothesis is advanced that adrenal medulla plays a pivotal role in the mechanism(s) underlying the adrenocortical secretagogue action of PACAP, being mineralocorticoid and glucocorticoid responses probably mediated by the release by chromaffin cells of catecholamine and ACTH or exclusively ACTH, respectively.

Adrenal Cortex↗

PubMed1995

Pancreatic polypeptide enhances plasma glucocorticoid concentration in rats: possible role in hypoglycemic stress.

The acute bolus intraperitoneal (i.p.) administration of pancreatic polypeptide (PP) dose-dependently enhanced the plasma concentration of corticosterone (PBC) in hypophysectomized/ACTH replaced rats, but not that of aldosterone. Minimal and maximal effective doses were 10(-12) and 10(-10) mol/rat, respectively, and maximal PBC increase occurred between 60 and 120 min after PP injection. Insulin (1 U/kg, i.p.) evoked a net decrease in the blood glucose concentration, and marked rises in the plasma levels of PP and PBC, that attained their maximum at 60 and 120 min, respectively. The effects of insulin were annulled by the simultaneous injection of 0.5 mg/kg atropine. The effects of 1 U/kg insulin and 10(-10) mol/rat PP on PBC were not additive; atropine did not affect PBC response to PP or PP plus insulin, though annulling that to insulin alone. Taken together these findings suggest that PP plays a physiologic role in the rat as modulator of the adrenal response to the insulin-induced hypoglycemic stress.

Aldosterone↗

PubMed1995

Effects of sex hormones on the steroidogenic activity of dispersed adrenocortical cells of the rat adrenal cortex.

The effect of 17 beta-estradiol and testosterone on glucocorticoid secretion were studied in vitro by using dispersed inner adrenocortical cells obtained from gonadectomized female and male rats. Independently of the sex of animals, estradiol enhanced basal, but not ACTH-stimulated corticosterone (B) secretion; conversely, testosterone inhibited ACTH-stimulated, but not basal B output. HPLC analysis of steroid secreted demonstrated that estradiol induced comparable rises (53-62%) in basal pregnenolone (PREG) and total post-PREG secretion (progesterone, 11-deoxycorticosterone and B). Testosterone inhibited by about 30% ACTH-stimulated PREG production and by about 54% total post-PREG secretion (B was decreased to 56% of the control value, and other steroid hormones were below the limit of sensitivity of our assay system). These findings indicate that sex hormones directly affect rat adrenocortical secretion, mainly by acting on the rate-limiting step of steroidogenesis (i.e. the conversion of cholesterol to PREG); moreover, they suggest that testosterone is also able depress the activity of the enzymes operating distally to cholesterol side-chain cleavage.

Adrenal Cortex↗

PubMed1995

Effects of neuromedin-K on the rat hypothalamo-pituitary-adrenal axis.

The effects of neuromedin-K (NMK) on the rat hypothalamo-pituitary-adrenal (HPA) axis were studied both in vivo and in vitro. A subcutaneous injection of 1 nmol/100 g NMK evoked a rise in plasma ACTH level at 30 min, increased plasma corticosterone (B) concentration (PBC) at 60 and 120 min, and did not alter plasma aldosterone (ALDO) concentration (PAC). The administration of 3 nmol/100 g NMK induced a rise in plasma ACTH level at 120 min and a drop of PBC at 30 min; it increased PBC and PAC at 60 and 120 min. NMK did not affect basal B secretion of dispersed zona fasciculata/reticularis (ZF/R) cells, but markedly enhanced basal ALDO production by dispersed zona glomerulosa (ZG) cells (minimal and maximal effective concentrations were 10(-9) M and 10(-7) M). Video-imaging analysis showed that NMK (10(-8) M) increased intracellular Ca2+ concentration in dispersed ZG cells, but not in ZF/R ones. These findings indicate that NMK exerts a complex modulatory action on the rat HPA axis: low doses of NMK appear to evoke a transient stimulation of ACTH release, while high doses seem to exert a short-term inhibition of glucocorticoid synthesis followed by the compensatory hypersecretion of ACTH; moreover, elevated doses of NMK also exert a strong ALDO secretagogue action by acting directly on the ZG cells.

Adrenal Glands↗

PubMed1995

Evidence that endogenous substance-P (SP) is involved in the maintenance of the growth and steroidogenic capacity of rat adrenal zona glomerulosa.

A 7-day intraperitoneal infusion with the specific SP antagonist magnitude of D-Pro4,D-Trp7,9-SP4-11 (SP-A; 0.3 nmol.kg-1.min-1) significantly lowered plasma aldosterone (ALDO) concentration and caused atrophy of adrenal zona glomerulosa (ZG) and its parenchymal cells. Dispersed ZG cells from SP-A-infused rats displayed a marked decrease in both their basal and maximally agonist-stimulated ALDO production. The simultaneous infusion of rats with SP (0.03 nmol.kg-1.min-1) completely annulled all these effects of SP-A. The plasma levels of ACTH and corticosterone, and the morphology of adrenal zona fasciculata were not affected by SP-A or SP-A plus SP infusion. These findings suggest that endogenous SP is specifically involved in the positive control of growth and secretion of the rat ZG.

Aldosterone↗

PubMed1995

Adrenal medulla is involved in the aldosterone secretagogue effect of substance P.

Substance P (SP) increased aldosterone secretion of rat adrenal slices, but not of isolated zona glomerulosa cells, and this effect was annulled by two specific antagonist of SP (SP-A). Both tissue preparations displayed an aldosterone secretory response to isoprenaline (IP) that was blocked by l-alprenolol (AL). AL reversed the aldosterone response of adrenal slices to IP, SP, or IP plus SP, whereas SP-A only suppressed that to SP. Quarters of adrenocortical autotransplants, which are completely deprived of chromaffin cells, showed an aldosterone response to IP, but not to SP. These findings suggest that the mechanism underlying the aldosterone secretagogue action of SP probably involves the stimulation of catecholamine release by adrenal medulla chromaffin cells.

Adrenal Cortex↗

PubMed1995

Investigations on the acute effects of neuropeptides on the pituitary-adrenocortical function in normal and cold-stressed rats. I. Bombesin and neuromedin B.

The effects of a subcutaneous bolus injection of 2 micrograms bombesin (BM) or neuromedin B (NMB) on the function of the hypothalamo-pituitary-adrenocortical (HPA) axis were investigated in both normal and cold-stressed rats. The blood concentrations of ACTH, corticosterone (B) and aldosterone (ALDO) were measured by specific radioimmunoassays 1, 2 or 4 h after the neuropeptide administration. Cold stress strikingly enhanced plasma levels of ACTH, B and ALDO, and these rises lasted unchanged until 4 h. BM and NMB significantly elevated plasma concentrations of ACTH and B in both normal and stressed animals. In both groups of rats the level of circulating ALDO was not apparently affected by neuropeptides. In light of these findings the following conclusions can be drawn: (i) BM and NMB acutely activate the HPA axis, probably by acting via the same receptor; (ii) the mechanism underlying this effect of BM and NMB is independent of that involved in the cold stress-induced activation of the HPA axis; and (iii) the well-known acute ALDO secretagogue effect of ACTH is probably counteracted by a direct inhibitory action of BM and NMB on adrenal zona glomerulosa.

Adrenocorticotropic Hormone↗

PubMed1995

Investigations on the acute effects of neuropeptides on the pituitary-adrenocortical function in normal and cold-stressed rats. II. Neurotensin and neuromedin N.

The effects of a subcutaneous bolus injection of 2 micrograms neurotensin (NT) or neuromedin N (NMN) on the function of the hypothalamo-pituitary-adrenocortical axis were investigated in both normal and cold-stressed rats. The blood concentrations of ACTH, corticosterone (B) and aldosterone (ALDO) were measured by specific radioimmunoassays 1, 2 or 4 h after the neuropeptide administration. Cold stress enhanced plasma levels of ACTH, B and ALDO, and these rises lasted unchanged until 4 h. NT did not affect either basal or stress-stimulated plasma levels of ACTH and B, while it lowered the plasma ALDO concentration at 4 h in normal rats and increased it at 1 h in stressed animals. NMN did not change the basal plasma level of ACTH, but it did markedly raise blood levels of both B and ALDO; on the other hand, in cold-stressed rats NMN strongly depressed ACTH response and decreased B plasma concentration at 2 h, without evoking apparent changes in ALDO response. In light of these findings the following conclusions and hypotheses can be drawn and suggested: (i) NT and NMN, when administered at a relatively high dose, do not affect ACTH release in rats under basal conditions; (ii) NMN, but not NT, is able to prevent cold stress-induced stimulation of ACTH secretion, probably by inhibiting hypothalamic thermoregulatory centers; and (iii) NT and NMN exert direct adrenocortical antisecretagogue and secretagogue effects, respectively, which could explain the evident lack of correlation between the levels of circulating ACTH and the plasma concentrations of the main adrenal steroid hormones in both normal and stressed rats after neuropeptide administration.

Adrenocorticotropic Hormone↗

PubMed1995

Bacterial lipopolysaccharide stimulates glucocorticoid secretion in hypophysectomized rats.

The effect of an i.p. bolus injection of 200 micrograms.kg-1 bacterial lipopolysaccharide (LPS) on the plasma concentrations of ACTH and corticosterone (B) were studied in intact and hypophysectomized/ACTH replaced (Hx) rats. Hormonal blood levels were measured by RIA, 30, 60, 120, 180 and 240 min after the injection. The stress evoked by the vehicle i.p. injection provoked significant rises in ACTH and B blood levels at 30 and 60 min in intact rats, but not in Hx animals. In intact rats, LPS enhanced (over the respective control value) ACTH plasma level at 60, 120 and 180 min, and B plasma concentration at 120, 180 and 240 min. In Hx rats, LPS did not affect ACTH blood level, but raised B plasma concentration at 60, 120 and 180 min. B response to LPS at 120 min was completely annulled, in both intact and Hx rats, by the simultaneous administration of 25 nmol.kg-1 alpha-helical-CRH and corticotropin-inhibiting peptide that are competitive inhibitors of CRH and ACTH, respectively. The hypothesis is advanced that LPS may activate hypothalamo-pituitary adrenal axis in rats, by stimulating not only the central (hypothalamo-pituitary), but also the peripheral (intra-adrenal) branch of the CRH/ACTH system.

Adrenocorticotropic Hormone↗

PubMed1995

Effects of neurokinin-A on the rat hypothalamo-pituitary-adrenal axis.

The effects of neurokinin-A (NKA) on the rat hypothalamo-pituitary-adrenal (HPA) axis were studied in vivo and in vitro. A subcutaneous injection of 1 or 3 nmol/100 g NKA did not alter plasma ACTH concentration. The lower dose of NKA evoked a transient rise in plasma corticosterone (B) concentration (PBC) at 30 min, and did not change plasma aldosterone (ALDO) concentration (PAC). The higher dose of NKA increased PBC at 30 and 60 min, and PAC at 30, 60 and 120 min. NKA did not affect basal ALDO secretion of dispersed zona glomerulosa (ZG) cells, but it markedly enhanced basal B production by dispersed zona fasciculata/reticularis (ZF/R) cells (minimal and maximal effective concentrations were 10(-9) M and 10(-6) M). Video-imaging analysis showed that 10(-6) M NKA increased intracellular Ca2+ concentration in dispersed ZF/R cells, but not in ZG ones. These findings indicate that NKA exerts a stimulatory action on the rat adrenal secretory activity, which is independent of any effect on the pituitary ACTH release: the B secretagogue action seems to be due to a direct effect of NKA on ZF/R cells, while the ALDO secretagogue action is not direct. but probably mediated by factor(s) other than ACTH.

Adrenocorticotropic Hormone↗

PubMed1995

In-vitro and in-vivo studies of the effects of arginine-vasopressin on the secretion and growth of rat adrenal cortex.

Arginine-vasopressin (AVP) markedly increased basal aldosterone (ALDO) secretion by dispersed zona-glomerulosa (ZG) cells, and its effect was selectively reversed by V1-receptor antagonists (AVP-A1). Corticosterone (B) production by dispersed zona fasciculata (ZF) cells was not affected. The bolus intraperitoneal (i.p.) administration of AVP acutely raised the plasma concentrations of both ALDO and B in normal rats, but only that of ALDO in bilaterally adrenalectomized animals bearing regenerated adrenocortical autotransplants, which are deprived of medullary chromaffin cells. Accordingly, AVP raised ALDO and B secretions by adrenal slices (including both cortical and medullary tissues), and only ALDO production by autotransplant quarters. The B response of adrenal slices to AVP was blocked by alpha-helical-CRH and corticotropin-inhibiting peptide (two competitive inhibitors of CRH and ACTH, respectively), but not by 1-alprenolol (a beta-adrenoreceptor antagonist); ALDO response was not affected by any of these antagonists. A 7-day i.p. infusion with AVP increased the volume of ZG cells and ZG-like cells of autotransplants, as well as their basal and maximally angiotensin-II-stimulated ALDO secretory capacity; it also raised the volume, and basal and maximally ACTH-stimulated B secretory capacity of ZF cells, but it did not affect ZF-like cells of autotransplants. The simultaneous administration of AVP-A1 annulled all these effects of AVP. When infused alone, AVP-A1 caused a marked atrophy of ZG cells, coupled with a net drop in their steroidogenic capacity; however, AVP-A1 infusion did not change the morphology and function of either ZF cells or ZG-like and ZF-like cells of autotransplants. Taken together,, our findings allow us to draw the following conclusions: (i) AVP plays an important physiological role in the maintenance and stimulation of ZG growth and mineralocorticoid secretory activity in rats, the source of endogenous AVP exerting adrenoglomerulotropic action probably being adrenal chromaffin cells; and (ii) AVP indirectly stimulates the growth and glucocorticoid secretory activity of rat ZF cells, by activating intramedullary CRH/ACTH system; however, the physiological relevance of this effect of AVP appears to be doubtful.

Adrenal Cortex↗

PubMed1995

Effects of bombesin on the morphology and function of the rat adrenal cortex: comparison of the acute and chronic responses.

The acute and chronic effects of bombesin (BM) on the structure and function of rat adrenal cortex were investigated by morphometric and radioimmunological techniques. An intraperitoneal bolus injection of 2 micrograms/rat BM markedly raised plasma corticosterone (B) concentration (PBC). The intraperitoneal BM infusion (1 microgram/rat.h-1) for 1, 2 or 4 days evoked a notable increase in the number of adrenocortical cells, without inducing apparent changes in either PBC or B output by adrenal quarters. Since proliferation and expression of specialized functions are mutually exclusive states of cells, our findings suggest that the conspicuous stimulation of adrenocortical-cell proliferation evoked by BM infusion may be responsible for the apparent lack of effect of this treatment on B secretion.

Adrenal Cortex↗

PubMed1994

Neuropeptide K enhances glucocorticoid release by acting directly on the rat adrenal gland: the possible involvement of zona medullaris.

Neuropeptide K (NPK), a member of the kassinin-like tachykinin family, is contained in the rat hypothalamus and is known to stimulate pituitary ACTH release. The intraperitoneal bolus administration of NPK dose-dependently enhanced corticosterone blood level not only in intact rats, but also in hypophysectomized/ACTH replaced animals. NPK did not affect corticosterone secretion of dispersed rat adrenocortical cells; however, it concentration-dependently raised basal corticosterone production by decapsulated adrenal quarters (including both cortical and medullary tissues). Minimal and maximal effective concentrations were 10(-9) and 10(-8) M, respectively. 10(-8) M NPK potentiated corticosterone response of adrenal quarters elicited by 10(-12) M ACTH, but not that evoked by higher concentrations of ACTH. The direct corticosterone secretagogue effect of 10(-8) M NPK is annulled by 10(-6) M alpha-helical-CRH or corticotropin-inhibiting peptide, competitive inhibitors of CRH and ACTH, respectively. In light of these findings, the hypothesis is advanced that NPK exerts a direct stimulatory action on adrenocortical secretion and that the mechanism underlying this effect of NPK may involve the activation of the intra-medullary CRH/ACTH system.

Adrenal Cortex↗

PubMed1994

Effect of hypophysectomy on corticotropin-releasing hormone and adrenocorticotropin immunoreactivities in the rat adrenal gland.

It has previously been shown that rat adrenal zona medullaris possesses an interleukin-1 beta (IL-1 beta)-responsive peripheral branch of the CRH/ACTH system that duplicates the hypothalamopituitary central one (Mazzocchi et al., Mol. Cell. Neurosci. 4: 267, 1993). The intraadrenal content of corticotropin-releasing hormone (CRH) and adrenocorticotropin (ACTH) immunoreactivities (ir), as well as IL-1 beta-stimulated release of CRH-ir and ACTH-ir, increased in relation to the number of days elapsed from hypophysectomy; the effect of hypophysectomy required at least 48 h to become significant and reached its maximum after 72 h. The action of IL-1 beta on ACTH-ir release was annulled by simultaneous exposure to alpha-helical-CRH, an antagonist of CRH. ACTH infusion, at a rate restoring a normal blood level of the hormone, prevented the effect of hypophysectomy on intraadrenal concentrations of both CRH-ir and ACTH-ir; similarly, the hypophysectomy-evoked rise in intraadrenal ACTH-ir content was completely annulled by treating hypophysectomized rats with CRH or dexamethasone. Taken together our findings suggest that the elimination of the central branch of CRH/ACTH system induces a marked increase in the activity of the intraadrenal peripheral one. The hypothesis is advanced that the hypophysectomy-induced lowering of circulating ACTH and the consequent drop in the production of adrenal glucocorticoids enhances, via a classic negative feedback mechanism, gene expression of CRH and ACTH in adrenal medullary chromaffin cells.

Adrenal Medulla↗

PubMed1994

Effects of neuromedin U-8 on the secretory activity of the rat adrenal cortex: evidence for an indirect action requiring the presence of the zona medullaris.

The acute effect of increasing concentrations (from 10(-8) to 10(-6) M) of neuromedin U-8 (NMU-8) on steroid secretion of rat adrenal gland was investigated in vitro by high-pressure liquid chromatography. The production of the following steroids was measured: pregnenolone (PREG), progesterone (PROG), 11-deoxycorticosterone (DOC), corticosterone (B), 18-hydroxy-11-deoxycorticosterone (18OH-DOC), 18-hydroxycorticosterone (18OH-B) and aldosterone (ALDO). NMU-8 had no effects on either dispersed adrenocortical cells or fragments of adrenocortical autotransplants lacking medullary chromaffin cells. Conversely, NMU-8 exerted concentration-dependent secretagogue effects on adrenal slices, including both cortex and medulla. At all concentrations tested, NMU-8 increased the production of both PREG and total post-PREG steroids. The increase in total post-PREG steroid output induced by low concentrations of NMU-8 (10(-8) M) was due to similar rises in the production of non-18-hydroxylated steroids (PROG, DOC and B) and 18-hydroxylated hormones (18OH-DOC, 18OH-B and ALDO); conversely, that provoked by higher concentrations of the neuropeptide (10(-7) to 10(-6) M) was almost exclusively caused by the rise in the yield of 18-hydroxylated steroids. The stimulating effect of NMU-8 on PREG output was blocked by both alpha-helical-CRH and corticotropin-inhibiting peptide, which are competitive inhibitors of CRH and ACTH, respectively. The following conclusions have been drawn: (1) NMU-8 affects adrenal steroid secretion indirectly by acting on the medullary chromaffin cells, which in turn may paracrinally stimulate the cortical ones; (2) at all concentrations tested, NMU-8, by stimulating the intramedullary CRH/ACTH system, causes a net rise in the activity of the early rate-limiting step of steroidogenesis, with the consequent increase in the output of the entire spectrum of post-PREG steroids; and (3) at higher concentrations (over 10(-8) M), NMU-8 also elicits the release from chromaffin cells of a factor (not yet known) that specifically enhances 18-hydroxylase activity.

Adrenal Cortex↗

PubMed1994

Modulatory action of neurotensin on the pituitary-adrenocortical function in rats: evidence for an acute dose-dependent biphasic effect.

Adult female rats were sc injected with 0.6 or 1.2 nmol/100 g body wt of neurotensin (NT); control animals received a sc injection of saline vehicle. The plasma concentrations of ACTH, aldosterone and corticosterone were measured 1, 2 or 4 h after the injection. Our RIA estimates revealed that the lower dose of NT exerted a net stimulatory effect on the rat pituitary-adrenocortical function, that can be ascribed to the well-known NT-evoked enhancement of CRH release. Conversely, the higher dose of NT appeared to have a marked inhibitory effect on both pituitary ACTH release and adrenocortical secretion. The mechanism underlying this last action of NT remains to be elucidated.

Adrenal Cortex↗

PubMed1994

Proliferogenic effect of neurotensin (NT) and neuromedin-N (NMN) on the rat adrenal cortex: evidence that angiotensin-II mediates the effect of NMN, but not of NT.

NT and NMN, two biologically active peptides acting via the same specific receptor, are both able to stimulate in vivo the proliferative activity of rat adrenocortical cells. The present study aimed to investigate whether the mechanism underlying this effect of NT and NMN may involve an enhanced production of angiotensin-II (ANG-II), a potent adrenocortical proliferogenic factor. Metaphases per adrenal section were counted 120 min after vincristine injection. A bolus administration of ANG-II resulted in a marked increase in the number of metaphase-arrested cells 12, 24 and 48 h after the beginning of the experiment; the concomitant administration of saralasin (SAR), a competitive antagonist of ANG-II, completely blocked the proliferogenic effect of ANG-II. NT-evoked rise in the number of metaphases occurred 48 h after administration and was not influenced by the simultaneous SAR injection. On the contrary, NMN injection induced a burst of adrenocortical cell proliferation within 12 h, and this effect was prevented by SAR. These data suggest that ANG-II mediates the proliferogenic effect of NMN, but not that of NT.

Adrenal Cortex↗