Biomedical subjects

A Markowska

Publications and source records attributed to A Markowska.

At least 55 records · Page 3Linked to original sources

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

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↗

PubMed1994

Effects of neuromedin U (NMU)-8 on the rat hypothalamo-pituitary-adrenal axis. Evidence of a direct effect of NMU-8 on the adrenal gland.

A 6-day subcutaneous (s.c.) treatment of adult rats with NMU-8 (1.5 or 6 micrograms/100 g/day) increased the average volume of zona fasciculata cells and decreased the number of zona reticularis cells in the adrenal cortex. The lower dose of NMU-8 did not change blood ACTH concentration and adrenal weight, but it notably enhanced serum corticosterone level and basal corticosterone output by adrenal slices. ACTH blood level increased after ether stress in both control and NMU-8-treated rats, but stress-evoked rise in serum corticosterone was observed only in control rats. The higher dose of NMU-8 increased the level of circulating ACTH; however, it decreased adrenal weight and had no effect on serum corticosterone concentration and basal corticosterone output by adrenal slices. NMU-8 (10(-10)/10(-6) M) did not affect basal and ACTH-stimulated corticosterone yield by isolated adrenocortical cells, nor did it change their cytosolic Ca2+ concentration. NMU-8 (10(-8) M) markedly raised basal corticosterone secretion by adrenal slices (including cortex and medulla); higher concentrations of NMU-8 (10(-7)/10(-6) M) were ineffective on basal corticosterone secretion, but strongly inhibited the response to ACTH stimulation. On the ground of these findings it seems reasonable to suggest that NMU-8 exerts a biphasic effect on the function of the peripheral branch of the hypothalamo-pituitary-adrenal axis in rats: NMU-8 at low doses directly stimulates the function and growth of the adrenal cortex, while at high doses exerts a direct inhibitory action.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

PubMed1994

Evidence that endogenous vasoactive intestinal peptide (VIP) is involved in the regulation of rat pituitary-adrenocortical function: in vivo studies with a VIP antagonist.

The effect of a subcutaneous bolus injection of 2 micrograms magnitude of Ac,Tyr1,D-Phe2-GRF(1-29) amide, a specific VIP antagonist (VIP-A), on the hypothalamo-pituitary-adrenocortical (HPA) axis were investigated in both normal and ether- or cold-stressed rats. Blood concentrations of ACTH, aldosterone (ALDO) and corticosterone (B) were measured by specific RIA 1, 2 or 4 h after VIP-A injection. VIP-A administration to normal rats strikingly lowered the plasma concentration of ALDO, without significantly affecting those of ACTH and B. Ether and cold stresses notably raised the blood levels of ACTH, ALDO and B, and these rises lasted unchanged until 4 h. VIP-A did not affect the response of HPA axis to ether stress, but provoked a marked depression of that to cold stress. In light of these findings the following conclusions can be drawn: (i) endogenous VIP does not regulate HPA-axis function under basal conditions, but it plays a pivotal role in the mechanisms involved in the activation of HPA axis induced by cold exposure; and (ii) endogenous VIP exerts a tonic stimulatory action on ALDO secretion, probably by acting directly on the adrenal zona glomerulosa.

Adrenal Cortex↗

PubMed1994

Evidence that endogenous somatostatin (SRIF) exerts an inhibitory control on the function and growth of rat adrenal zona glomerulosa. The possible involvement of zona medullaris as a source of endogenous SRIF.

The effect of SRIF and its antagonist cyclo(7-aminoheptanonyl-Phe-D-Trp-Lys-Thr magnitude of Bzl)(SRIF-A) were studied in sham-operated and bilaterally adrenalectomized rats bearing ACTH- and angiotensin II (ANG-II)-responsive adrenocortical autotransplants. SRIF-A (10(-5) M) completely annulled SRIF (10(-6) M)-induced inhibition of ANG-II (10(-8) M)-evoked rise in aldosterone (ALDO) secretion by both dispersed zona glomerulosa (ZG) cells and autotransplant slices. A 7-day intraperitoneal infusion with SRIF (0.3 nmol.kg-1.min-1) significantly lowered plasma ALDO concentration (PAC) in both groups of animals, without affecting plasma renin activity and the plasma levels of ACTH and corticosterone. This treatment caused a marked atrophy of adrenal ZG and its parenchymal cells (without inducing any significant change in the zona fasciculata morphology), as well as of ZG-like cells of autotransplants. Isolated ZG cells and autotransplant slices from SRIF-infused rats evidenced a notable decrease in both their basal and maximally ACTH- or ANG-II-stimulated ALDO production. The simultaneous infusion of rats with SRIF-A (3 nmol.kg-1.min-1) completely reversed all these effects of SRIF. The prolonged infusion with SRIF-A alone caused, in sham-operated rats, a marked increase in PAC and a significant hypertrophy of ZG and ZG cells; basal and maximally-stimulated ALDO secretion of dispersed ZG cells was also notably raised. Conversely, SRIF-A infusion did not evoke any appreciable effect in autotransplanted rats. These findings suggest that endogenous SRIF is specifically involved in the negative control of the secretion and growth of the rat adrenal ZG. Since regenerated adrenocortical autotransplants, which are responsive to SRIF but not to SRIF-A infusion, are completely deprived of chromaffin cells, the hypothesis is advanced that adrenal zona medullaris may be the source of endogenous SRIF regulating ZG function.

Adrenal Cortex↗

PubMed1994

Effects of cyclosporine-A on steroid secretion of dispersed rat adrenocortical cells.

The acute effect of cyclosporine-A (CSA), a potent immunosuppressive agent, on the secretory activity of dispersed rat adrenocortical cells was investigated. The production of the following steroid hormones was assayed by high performance liquid chromatography: pregnenolone (PREG), progesterone (PROG), 11-deoxycorticosterone (DOC), corticosterone (B), 18-hydroxy-11-deoxycorticosterone (18OH-DOC), 18-hydroxycorticosterone (18OH-B) and aldosterone (ALDO); B and ALDO outputs were also measured by radioimmunoassay. Low concentrations of CSA (0.1-0.2 mg/ml) enhanced basal, but not ACTH- or angiotensin-II (ANG-II) 10(-8) M-stimulated, secretions of PREG, non-18-hydroxylated steroids (PROG, DOC and B) and 18-hydroxylated steroids (18OH-DOC, 18OH-B and ALDO) of both zona glomerulosa (ZG) and zonae fasciculata and reticularis (ZF/ZR) cells. Middle concentrations of CSA (from 0.3 to 0.5 mg/ml) did not affect PREG yield, nor did they alter basal and ACTH-stimulated post-PREG output of both ZG and ZF/ZR cells; however, they elicited a marked decrease in ANG-II-enhanced production of 18-hydroxylated steroid by AG cells. Concentrations of CSA higher than 0.5 mg/ml strikingly reduced either basal and agonist-stimulated over-all steroidogenesis of both ZG and ZF/ZR cells. These findings suggest that CSA at low concentrations strongly stimulates the conversion of cholesterol to PREG (i.e. the rate-limiting step of steroidogenesis), while at middle concentrations it did not affect this early step, but specifically interferes with the intracellular events which transduce the stimulatory signal of ANG-II on the late steps of mineralocorticoid production (i.e. the conversion of B to ALDO). At higher concentrations, CSA probably exerts a cytotoxic effect.

Adrenal Cortex↗

PubMed1994

Different effects of neurotensin and neuromedin-N on the proliferative activity of rat adrenal cortex.

Evidence indicates that neurotensin (NT) and neuromedin-N (NMN) exerts an adrenocorticotropic effect in the rat. The present study aimed to investigate whether these neuropeptides are able to stimulate the proliferation of rat adrenocortical cells in vivo and to compare their mode of action. Adrenocortical proliferative activity was assessed by the metaphase-arrest technique and metaphases were counted per medulla-containing adrenal section. A bolus administration of NT (3 micrograms/rat) resulted in a significant increase in the number of metaphases in both zona fasciculata and the entire cortex, an effect observed 48 h after the injection. The administration of NMN (3 micrograms/rat) induced a notable rise in the number of metaphases in the zona fasciculata and the entire cortex within 12 h, followed by a subsequent drop after 24 h and a return to normal values at 48 h. These findings indicate that NT and NMN enhance rat adrenal growth in vivo acting via different mediators.

Adrenal Cortex↗

PubMed1994

Neuromedins and their involvement in the regulation of growth, structure and function of the adrenal cortex.

Current data on the synthesis and the mechanism of action of neuromedins on adrenal cortex are presented. The localization of these biologically-active peptides in all components of the hypothalamopituitary-adrenal axis as well as their action on the adrenal cortex both in vivo and in vitro suggest their involvement in the regulation of growth, structure and function of the adrenal cortex. Neuromedins may exert both direct and indirect effect on the adrenal cortex. Direct effect is proven by the stimulation of glucocorticoid synthesis by adrenocortical cells in culture (NMK, NML) while indirect effects may be mediated by ACTH, vasopressin (aldosterone secretagogue effect) and angiotensin (prompt proliferative response) or by substances of medullary origin. The last mechanism of action is well documented for NMU.

Adrenal Cortex↗

PubMed1994

Age-dependent changes in the function and morphology of mitochondria of rat adrenal zona fasciculata.

The function and morphology of adrenal zona-fasciculata (ZF) mitochondria were studied in 4-, 10- and 16-month-old rats, since in this species ageing causes a marked decline in glucocorticoid secretion coupled with high levels of circulating ACTH. Dispersed intact ZF cells displayed a significant age-dependent impairment of their basal pregnenolone (PREG) secretion, but isolated ZF mitochondria showed an increased capacity to convert cholesterol to PREG (the first rate-limiting step of steroid synthesis). These data are in keeping with the contention that the age-related deficit of rat ZF secretion is located prior to the activity of intramitochondrial cholesterol side-chain cleaving enzymes (cytochrome-P450scc). Stereology showed a notable age-dependent increase in the number of mitochondria per unit cell-volume, coupled with a marked decrease in their average volume. The width of the mitochondrial intermembrane space remained unchanged, but its average volume strikingly decreased. This last finding fits well with the enhanced capacity of mitochondria to produce PREG, since intermembrane space is an aqueous barrier to the translocation of free cholesterol from the outer membrane to the cristae, where cytochrome-P450scc is located. In conclusion, the hypothesis is advanced that all these age-related functional and morphological mitochondrial changes are an ACTH-dependent compensatory response enabling ZF cells to partially counteract their decreased glucocorticoid secretory capacity, which in turn is due to the impaired utilization of intracytoplasmic stores of cholesterol esters.

Aging↗

PubMed1993

Evidence that an extrahypothalamic pituitary corticotropin-releasing hormone (CRH)/adrenocorticotropin (ACTH) system controls adrenal growth and secretion in rats.

Within two weeks, hypophysectomy induced in rats a striking decrease in the level of circulating ACTH (the concentration of which was at the limit of sensitivity of our assay system), coupled with a net reduction in the plasma corticosterone concentration and an evident adrenal atrophy. Zona fasciculata, the main producer of glucocorticoids, was decreased in volume, due to a lowering in both the number and average volume of its parenchymal cells. Subcutaneous ACTH infusion (0.1 pmol.min-1), administered during the last week following hypophysectomy, restored the normal blood level of ACTH and completely reversed all effects of hypophysectomy on the adrenals. Subcutaneous infusion for one week with alpha-helical-CRH or corticotropin-inhibiting peptide (1 nmol.min-1), which are competitive inhibitors of CRH and ACTH, evoked a further significant lowering of plasma corticosterone concentration and markedly enhanced adrenal atrophy in hypophysectomized rats. These findings strongly suggest that an extrahypothalamic pituitary CRH/ACTH system may be involved in the maintenance of the growth and steroidogenic secretory activity of the rat adrenal cortex.

Adrenal Glands↗

PubMed1993

Effects of neuromedin-N on the pituitary-adrenocortical axis of dexamethasone-suppressed rats.

Neuromedin-N (NMN) (6 micrograms/100 g body weight for 2 d) partially reversed the dexamethasone (Dx)-induced inhibition of ACTH release and the consequent adrenal atrophy and decrease in glucocorticoid (corticosterone) plasma concentration in rats. Dx administration did not alter the level of circulating mineralocorticoid (aldosterone), but NMN (2 or 6 micrograms/100 g body weight for 2 d) significantly increased it. These findings suggest that the mechanism underlying the glucocorticoid (but not the mineralocorticoid) secretagogue action of NMN involves the stimulation of hypophyseal ACTH release. The hypothesis is advanced that the potent mineralocorticoid secretagogue effect of NMN may be mediated either by a direct action on zona glomerulosa cells or by the enhanced release of other regulatory peptides exerting aldosterone stimulating effect.

Adrenocorticotropic Hormone↗

PubMed1993

Evidence that endogenous arginine-vasopressin (AVP) is involved in the maintenance of the growth and steroidogenic capacity of rat adrenal zona glomerulosa.

A 7-day subcutaneous infusion with the AVP antagonist [Deamino-Pen1, Val4, D-Arg8]-vasopressin (AVP-A; 3 nmol.kg-1 x min-1) significantly lowered plasma aldosterone concentration in rats, without affecting the plasma levels of ACTH and corticosterone. Prolonged AVP-A treatment caused a marked atrophy of adrenal zona glomerulosa (ZG) and its parenchymal cells, without inducing any significant change in zona fasciculata morphology. Isolated ZG cells from AVP-A-infused rats evidenced a notable decrease in both their basal and maximally-stimulated aldosterone production. The simultaneous infusion of rats with AVP (3 nmol.kg-1 x min-1) completely reversed all these effects of AVP-A. These findings suggest that endogenous AVP may be specifically involved in the maintenance of the growth and steroidogenic capacity of rat adrenal ZG. Moreover, they seem to indicate that under basal conditions the pituitary-adrenal-glucocorticoid axis is independent of AVP release.

Adrenocorticotropic Hormone↗

PubMed1993

Effects of bombesin and neuromedin-B on the proliferative activity of the rat adrenal cortex.

Bombesin (BM) and neuromedin-B (NMB) exert similar biological effects, acting via two functionally distinct BM-receptor subtypes. The present study aimed to investigate whether BM and NMB stimulate the proliferation of rat adrenocortical cells and to compare their mode of action. Adult female rats were treated with a single subcutaneous dose of 3 micrograms BM or NMB. Adrenocortical proliferative activity was assessed by the metaphase-arrest technique. BM administration resulted in a marked increase in the number of metaphases in zona glomerulosa (ZG) and zona fasciculata (ZF), and in the entire cortex. This increase appeared 24 h after injection in the ZG, and after 48 h in the ZF. NMB administration, on the other hand, caused a prompt increase in the number of metaphases in the ZG and entire cortex at 12 h, followed by a subsequent drop below the control level at 24 and 48 h of experiment. These findings indicate that BM and NMB enhance the proliferative activity of rat adrenocortical cells acting via different receptors or different mediators.

Adrenal Cortex↗

PubMed1992

Analysis of the preventive action of ACTH on dexamethasone-induced adrenocortical atrophy in the rat.

Adult female rats were treated for 4 or 6 days consecutively with dexamethasone (Dx; 100 micrograms kg-1 day-1) alone or with ACTH (100 micrograms kg-1 day-1) for 2, 4 or 6 days. After 2 days of ACTH administration, zona fasciculata cells increased in volume, and the blood concentration of corticosterone was raised. Basal corticosterone secretion by adrenal slices appeared to be enhanced by ACTH treatment only when calculating per adrenal pair (and not per unit wt of adrenals). A significant increase in the number of metaphase cells was observed after only 4 days of ACTH administration. It is suggested that (1) the first action of ACTH on Dx-suppressed rats is to induce the hypertrophy of adrenocortical cells; (2) the steroidogenic capacity of adrenocortical cells is directly proportional to their average volume; and (3) the stimulatory effect of ACTH on the proliferative activity of adrenocortical cells is subsequent to the stimulation of their specialized functions.

Adrenal Cortex↗

PubMed1991

Basal forebrain cholinergic system: a functional analysis.

This chapter has been organized empirically, focusing on the types of approaches that have been taken to understand BFCS function. This approach reflects the state of our knowledge about the behavioral and psychological functions of the BFCS. Considerable information has been gathered in the very short time that the BFCS has been the object of intense investigation. The results from the neurotoxic lesions and from the HACU studies provide some points of consistency and some puzzling differences. Both approaches to the study of basal forebrain function suggest that the MSA is involved in tasks that require spatial working memory; MSA lesions impaired choice accuracy, and HACU in the HIP was increased after performance. The pattern of results in simpler tasks is more difficult to interpret. In a left-right reference memory discrimination in a T-maze, MSA lesions did not impair acquisition or performance, whereas HACU in the HIP was activated during performance. This pattern of results suggests that although the MSA is engaged during this type of task, its activity is not necessary for normal performance. These, and other comparisons indicate the need for a systematic analysis of task demand (Olton, 1989b). Parametric manipulations of different task demands in a systematic fashion can indicate the extent to which the BFCS is involved in the function associated with each parametric manipulation. Ultimately, of course, the organization of this material should focus on particular psychological functions, rather than the techniques and procedures used to gather the information. Achieving this goal is going to require careful attention to the design of behavioral experiments so that definitive conclusions can be made about the extent to which the BFCS is involved in a given psychological function. A systematic application of task analysis can achieve this goal (Olton, 1986, 1989a, 1989b). For example, BFCS lesions in rats impair choice accuracy in spatial working memory tasks, and performance in these tasks engages the HACU system, at least in the HIP. If the spatial functions of this task involve the BFCS, then a nonspatial version of the task should produce a different pattern of results. If the spatial nature of the task is unimportant for BFCS function, then a nonspatial version of the task should produce the same results. By systematically changing one characteristic of the task at a time, the contribution of each component can be assessed.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗

PubMed1991

Comparison of the effects of neurotensin and ACTH on the pituitary-adrenocortical axis of dexamethasone-suppressed rats.

Neurotensin (NT) (12-48 micrograms/kg-1/day-1, for 2 days, s.c.), like ACTH (60 micrograms/kg-1/day-1, for 2 days, s.c.), counteracted the dexamethasone (Dx)-induced (120 micrograms/kg-1/day-1, for 4 days, s.c.) adrenal zona-fasciculata cell atrophy. NT notably raised, in Dx-suppressed rats, the plasma concentration of ACTH, which reached about that found after exogenous ACTH administration. However, at variance with ACTH, NT did not enhance either plasma corticosterone (B) level or B production by adrenal quarters in vitro. The conclusion is drawn that NT modulates the function of the rat pituitary-adrenocortical axis, by simultaneously stimulating hypophyseal ACTH release and inhibiting steroidogenesis at the adrenal level.

Adrenocorticotropic Hormone↗

PubMed1991

Individual differences in aging: behavioral and neural analyses.

Aged populations have remarkable variability in recent memory and cognitive mapping. Although some individuals may have substantial age-related impairments, others perform almost as well as young individuals. This paper reviews the relevant data on aged rats and indicates two challenges for biomarkers of aging. The first is to provide an appropriate quantitative description of these individual differences. The second is to use them effectively as markers for age-related changes in psychological functions and their neural substrates.

Aging↗