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S R Bornstein

Publications and source records attributed to S R Bornstein.

At least 19 recordsLinked to original sources
PubMed1995

Long-term effect of octreotide in acromegaly on insulin resistance.

An important feature of acromegaly is a reduced action of insulin on hepatic gluconeogenesis and peripheral glucosal disposal. Octreotide (SMS) exerts complex effects on hormonal and metabolic regulations affecting glucose homeostasis. Eight patients with active acromegaly despite surgical intervention (age 44.8 +/- 3.5 years, BMI 27.3 +/- 1.6 kg/m2, lean body mass (LBM) 70 +/- 3.2%, blood glucose 5.24 +/- 0.26 mmol/l, HbA1c < or = 6.5%) were investigated before and after 6 months of treatment with SMS in an open trial. SMS was injected sc. at a dosage between 100-200 micrograms t.i.d. Mean GH and IGF1 levels during SMS therapy were significantly reduced (GH 9.6 +/- 1.9 ng/ml vs. 4.9 +/- 1.3 ng/ml, p < 0.05; IGF1 729.5 +/- 84 ng/ml vs. 415 +/- 49 ng/ml, p < 0.05). OGTT and euglycaemic-clamp-studies were performed before and after 6 months of SMS treatment. The glucosal disposal rate on average (insulin infusion rate 40 mU/m2/min) was not significantly changed following SMS treatment (McLBM before 3.60 +/- 0.38, after 3.95 +/- 0.41 mg/kg LBM/min). There was a positive correlation (r = 0.620) between the individual change of IGF1 and the change of McLBM. Additionally there was no significant difference of serum basal insulin levels (0.19 +/- 0.01 vs. 0.23 +/- 0.06 nmol/l) as well as basal C-peptide levels (0.79 +/- 0.07 vs. 0.47 +/- 0.04 nmol/l) before and with SMS treatment. We therefore conclude that long-term treatment of acromegalic patients with SMS, which achieves a successful reduction of GH and IGF1 levels, does not always guarantee a significant improvement in glucose metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1995

IL-1 is expressed in human adrenal gland in vivo. Possible role in a local immune-adrenal axis.

IL-1 is an important mediator in the dialogue between the immune system and the hypothalamo-pituitary-adrenal axis. A direct influence of IL-1 upon adrenal steroidogenesis has been demonstrated in experimental animals. We therefore designed a study to see if IL-1 is expressed within the normal human adrenal gland. The combination of in situ hybridization and specific immunostaining to IL-1 beta was eminently suited to demonstrate both mRNA and protein production. The specific immunostaining of the different cells combined with in situ hybridization (IL-1) allowed us to identify the exact cellular source of IL-1. IL-1 mRNA occurred in the zona reticularis in 17 alpha-hydroxylase positive steroid cells surrounding the adrenomedullary cells. Some CD68+ macrophages in this zona showed a positive signal. A weak signal was seen to IL-1 mRNA in few chromaffin cells, while IL-1-like immunoreactivity was more frequent. We conclude that in the normal situation in man IL-1 is mainly expressed in specialized cortical cells. The occurrence of the major glucocorticoid inducing factor in the normal human adrenal gland itself provides evidence for an autocrine or paracrine reaction under physiological conditions.

Adrenal Glands↗
PubMed1995

Plasma catecholamines in patients with Addison's disease.

BACKGROUND AND OBJECTIVE: Two endocrine tissues are present within the adrenal gland: the steroid producing cortical cells and the catecholamine producing chromaffin cells. Glucocorticoids occur in high concentrations in the adrenal medulla. In vitro, glucocorticoids have been shown to induce the enzyme phenyl-N-methyl-transferase which is necessary for the production of adrenaline in adrenal medullary cells. The purpose of this study was to evaluate the possible significance of a local glucocorticoid effect on adrenomedullary function. DESIGN: Plasma catecholamine levels were measured in patients with autoimmune Addison's disease where local production of corticosteroids is deficient in the presence of intact chromaffin tissue. MEASUREMENTS: Catecholamines were measured by high pressure liquid chromatography and ACTH, renin and adrenal steroids by radioimmunoassay. PATIENTS: Nineteen Addisonian patients (9 females, 10 males) were treated according to a standard regime with oral cortisone acetate (37.5 mg/day) and fludrocortisone (0.1 mg/day). All patients were clinically well. RESULTS: Mean plasma adrenaline in patients with Addison's disease was significantly reduced compared to a sex and age matched control group (males (n = 10) 143 +/- 36 pmol/l, controls (n = 27) 303 +/- 30 pmol/l, P < 0.01; females (n = 9) 77 +/- 25 pmol/l, controls (n = 27) 293 +/- 21 pmol, P < 0.001). The noradrenaline:adrenaline ratio was clearly higher in patients with Addison's disease (males 24 +/- 4, controls 9 +/- 1, P < 0.01; females 45 +/- 6, controls 9 +/- 1, P < 0.01). CONCLUSION: We conclude that the physiologically high local glucocorticoid concentration may be responsible for normal adrenaline production under basal conditions.

Addison Disease↗
PubMed1994

Macrophages within the human adrenal gland.

There is increasing evidence for an immune-adrenal interaction in which macrophages may play an important role. However, few data are available with respect to a human intra-adrenal macrophage system. In this study, we have investigated the density, distribution and phenotype of human adrenal macrophages using monoclonal antibodies. Macrophages are localized in all zones of the adrenal gland. These cells exhibit the phenotype of the phagocytotic macrophage compartment (CD11c+, KiM8+). At the ultrastructural level, macrophages are frequently attached to the endothelial wall, but also lie in direct contact with cortical and chromaffin cells. This investigation reveals the cellular basis for the possible role of macrophages in the local immune-neuroendocrine axis.

Adrenal Glands↗
PubMed1994

Sympathoadrenal regulation of adrenal androstenedione release.

The effects of epinephrine and of splanchnic nerve activation on adrenocortical androstenedione release were studied in intact isolated perfused pig adrenals with preserved nerve supply. In addition, long-term effects of epinephrine were characterized in bovine adrenocortical cells in primary culture. To investigate the contact zones of the androgen-producing cells of the zona reticularis with the catecholamine producing cells of the adrenal medulla, cortical cells were immunostained for cytochrome P450 side chain cleavage (P450SCC). Perfusion of the isolated adrenals with epinephrine (10(-7) to 10(-5) M) stimulated androstenedione release in a dose-dependent manner. At a concentration of 10(-6) M, epinephrine provoked an increase to 179.11 +/- 16.14% of basal secretion (p < 0.05). Electrical stimulation of the splanchnic nerves led to an increase to 151.5 +/- 9.24% of basal values (p < 0.05). Epinephrine (10(-6) M) reached 40% and activation of the splanchnic nerves 26% of the stimulatory effect of ACTH at a physiological concentration (10(-10) M). The alpha-agonist phenylephrine had no effect on androstenedione release. In cell cultures, epinephrine stimulated the release of androstenedione in a dose-dependent manner with an ED50 of 0.75 x 10(-6) M. The maximal effect was reached at 10(-5) M with 8.92 +/- 0.66 pmol androstenedione/dish/24 h; the basal secretion was 1.44 +/- 0.54 pmol/dish/24 h. The epinephrine-stimulated androstenedione release was abolished by the beta-adrenergic antagonist propranolol while the alpha-adrenergic antagonist phentolamine had no effect. Immunohistochemical staining of paraffin sections of bovine and porcine adrenals for P450SCC revealed that zona reticularis and zona medullaris are closely interwoven.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1994

Interleukin-1 regulates corticosterone secretion from the rat adrenal gland through a catecholamine-dependent and prostaglandin E2-independent mechanism.

Studies from this and other laboratories have shown that interleukin-1 alpha (IL-1 alpha) stimulates corticosterone and prostaglandin (PG) release from primary cultures of rat adrenal cells. A previous report from our laboratory (1) indicated involvement of the alpha-adrenergic system in IL-1 alpha-stimulated corticosterone secretion from primary cultures of rat adrenal cells. The present experiments were conducted to determine the role of catecholamines and eicosanoids in IL-1-stimulated corticosterone release from primary rat adrenal cells. Primary adrenal cells were incubated for 24 h at 37 C with IL-1 alpha (10 nM), medium, or the appropriate agonist. After incubation, the supernatant was removed and assayed for epinephrine, prostaglandin E2 (PGE2), and corticosterone concentrations. At this time, untreated adrenal cells were fixed for immunohistochemical staining with a specific antirat tyrosine hydroxylase antibody. The results indicate that the primary adrenal cells contained 3.1 +/- 0.45% tyrosine hydroxylase-positive cells. On the ultrastructural level, the chromaffin cells were found to be in direct cellular contact with cortical cells. IL-1 alpha significantly increased (P < 0.05) epinephrine, PGE2, and corticosterone levels above those in medium-treated controls from primary adrenal cells. In the presence of the alpha-adrenergic antagonist phentolamine (10 microM), IL-1 alpha-stimulated (P < 0.05) corticosterone release was inhibited, whereas IL-1 alpha-induced PGE2 release was not affected. Conversely, the presence of the cyclooxygenase inhibitor indomethacin (10 microM) significantly inhibited IL-1 alpha-induced PGE2 secretion without altering the effect of IL-1 alpha on corticosterone release. Inhibitors of the 5-lipoxygenase system (10 microM CGS 8518) and the lipoxygenase and cytochrome P450 monooxygenase systems (10 microM nordihydroguaiaretic acid) did not effect IL-1 alpha-induced corticosterone or PGE2 release. These observations indicate that IL-1 alpha stimulates corticosterone release through an alpha-adrenergic mechanism that is independent of PGE2 release from primary rat adrenal cells.

Adrenal Glands↗
PubMed1994

Intimate contact of chromaffin and cortical cells within the human adrenal gland forms the cellular basis for important intraadrenal interactions.

A new role for the adrenal medulla as a regulator of adrenocortical function has been postulated. However, there has been no idea as to how such a cellular interaction within the human adrenal gland could take place. In this study we were able to demonstrate with the help of specific immunostaining of cortical and chromaffin cells, respectively, that the two endocrine systems are interwoven with each other to an astonishing degree. Protrusions, clusters, islets, and single cortical cells were made visible by immunostaining with an antibody against 17 alpha-hydroxylase cytochrome P450 enzyme. They occurred diffusely within the entire adrenal medulla, providing ample contact zones for paracrine interactions. Specific immunostaining for the neuroendocrine protein chromogranin-A identified the occurrence of chromaffin cells within all three zones of the human adrenal cortex, including the zona glomerulosa. In an ultrastructural analysis, cortical and chromaffin cells were found in all zones in direct apposition, providing the possibility for direct intercellular exchange. The close morphological colocalization of cortical and chromaffin cells revealed in this study may constitute the basis for the growing evidence of relevant intraadrenal paracrine mechanisms within the human adrenal gland.

Adrenal Cortex↗
PubMed1994

Interleukin-6 stimulates the hypothalamus-pituitary-adrenocortical axis in man.

A recent study in humans, animal studies, and in vitro data have suggested that interleukin-6 (IL-6) stimulates the secretory activity of the hypothalamus-pituitary-adrenocortical (HPA) axis. In a phase II study, one female and six male patients with metastatic renal cell carcinoma received IL-6 to evaluate a possible antitumor effect of IL-6. This offered the possibility of investigating the influence of IL-6 on the HPA axis in man. The subjects were studied 1 day before, on day 1, and on day 21 of IL-6 therapy (150 micrograms administered sc every day at 0900 h). Blood samples were taken at 0900, 1100, 1300, 1600, and 2000 h the day before, on day 1 of IL-6 therapy, 24 h after the first IL-6 injection, and on day 21 of IL-6 treatment. Plasma ACTH and cortisol levels promptly followed the rise of IL-6, which peaked 4 h after administration. They were significantly (P < 0.05) higher at 1100 and 1300 h on day 1 of IL-6 therapy compared with the corresponding plasma levels the day before IL-6 treatment. Cortisol concentrations remained significantly increased at 1600 and 2000 h after IL-6 administration. Twenty-four hours after the first IL-6 administration, IL-6, ACTH, and cortisol levels had reached preinjection values. Although plasma cortisol levels were similar on days 1 and 21, ACTH levels were lower on day 21 (than on day 1), but significantly elevated at 1100 h compared with levels on the day before the first IL-6 injection. Results confirming the very recent data of another study demonstrate a stimulating effect of IL-6 on the HPA axis in man. They support the notion that IL-6 is one of the cytokines involved in the interaction between the immune system and the HPA axis.

Adrenal Cortex↗
PubMed1994

Interleukin-6 messenger ribonucleic acid expression in human adrenal gland in vivo: new clue to a paracrine or autocrine regulation of adrenal function.

Interleukin-6 (IL-6) is an important mediator in the interaction of the hypothalamo-pituitary-adrenal axis with the immune system. Recently, a direct influence of IL-6 on adrenal steroidogenesis has been demonstrated. Therefore, we designed a study to determine whether IL-6 is expressed within the normal human adrenal gland. The combination of in situ hybridization and specific immunostaining was eminently suited to identify the cell types producing IL-6. IL-6 messenger ribonucleic acid occurred in the inner zone of the adrenal cortex in anti-17 alpha-hydroxylase-positive steroid cells. Also, CD68-positive macrophages in the zona reticularis showed a positive signal. No reaction was seen in chromaffin cells. We conclude that under normal conditions, IL-6 is expressed in specialized adrenocortical cells. Therefore, IL-6 may play an important role as a paracrine or autocrine factor in a local immune-adrenal interaction.

Adrenal Glands↗
PubMed1993

Vasoactive intestinal peptide (VIP) stimulates androstenedione release in isolated perfused pig adrenals.

The effect of the vasoactive intestinal peptide (VIP) on adrenal androstenedione release was investigated in isolated perfused pig adrenals. Our system allowed a direct comparison with the effect of ACTH, gonadotropins and proopiomelanocortin 79-96, which has been suggested to be the specific cortical androgen stimulating hormone (CASH). VIP 10(-8) M provoked a threefold increase of androstenedione release which was similar to the effect of ACTH at a physiological concentration of 10(-10) M. Gonadotropins at a perfusate concentration of 0.5 I.U. weakly but significantly increased androstenedione output, the response amounting to 32% of that elicited by ACTH or VIP. Perfusion of the adrenals with CASH at concentrations of 10(-11) to 10(-8) M did not affect the release of adrenal androstenedione. VIP appears to be a modulator of adrenal androgen release which might be involved in a local neuroendocrine control of adrenal androgen secretion.

Adrenal Glands↗
PubMed1993

Atrial natriuretic peptide-like immunoreactive material (ANP-LI) is released from the adrenal gland by splanchnic nerve stimulation.

We investigated the release of atrial natriuretic peptide-like immunoreactive material (ANP-LI) after splanchnic nerve stimulation of isolated perfused adrenal glands. Electrical stimulation of the splanchnic nerves caused a statistically significant increase of ANP-LI (186 +/- 12 pg.min-1; p < 0.05) at 5 min. after stimulation. The integrated ANP-LI release after stimulation was amounted to 354 +/- 6.8% over basal. The regulation of ANP through the sympathoadrenal system may indicate an important role of ANP in adrenal steroidogenesis.

Adrenal Glands↗
PubMed1992

Structure and dynamics of adrenal mitochondria following stimulation with corticotropin releasing hormone.

The mitochondria of rat adrenals were investigated qualitatively and quantitatively in different functional states of the adrenal cortex. Following stimulation of the animals with corticotropin releasing hormone (CRH), the corticosterone serum levels reached a maximum 1 hour after stimulation with CRH. The amount of inner mitochondrial membrane within the zona fasciculata increased showing a biphasic time course, with a first maximum 2 hours and a second maximum 8 hours after stimulation. In contrast, a significant rise of mitochondrial volume occurred only 24 hours after CRH stimulation. Therefore, the dense vesicularization of mitochondrial cristae may constitute an early process to enhance the steroidogenic capacity of these cells. Within cells of the transition zone between zona glomerulosa and zona fasciculata, we could depict a special type of mitochondria with characteristic crescent-like cristae only seen after stimulation with CRH. This type of mitochondria may represent an intermediate form between mitochondria of zona glomerulosa and zona fasciculata underlining the impressive transformational capacity of adrenocortical mitochondria. After hypophysectomy, zona fasciculata cells contained mitochondria with tubular inner membranes, representing a hypofunctional state. In contrast, the hypofunctional state after hypophysectomy and the hyperfunctional state after stimulation of the adrenal cortex via CRH injection did not appear to correlate with the morphology of mitochondria from the zona reticularis and adrenal medulla.

Adrenal Cortex↗
PubMed1992

Ultrastructural evidence for a paracrine regulation of the rat adrenal cortex mediated by the local release of catecholamines from chromaffin cells.

The adrenal glands of perfusion fixed rats were investigated by light and electron microscopy. Within the rat adrenal cortex occurred rays and islets of chromaffin cells which were in close contacts with cortical cells on the electron microscopical level. We achieved to catch the process of exocytosis from a chromaffin cell located within the zona glomerulosa in direct apposition with an adrenocortical cell. The documentation of an exocytotic process from a chromaffin cell neighbouring a cortical cell provides direct evidence in support of a paracrine regulation of the cortex mediated by chromaffin cells.

Adrenal Cortex↗
PubMed1992

Role of ovarian sex steroids in the regulation of thyrotropin (TSH) secretion of hypogonadal women.

The exact role of ovarian sex steroids in the neuroendocrine regulation of thyrotropin (TSH) release in women can only be accurately assessed in the absence of any considerable ovarian sex steroid feedback upon the hypothalamic-pituitary unit. Consequently, the unstimulated episodic and thyrotropin-releasing hormone (TRH) stimulated TSH secretion was evaluated in postmenopausal women before and during sequential ovarian sex steroid replacements. Seven euthyroid women (mean age: 59.4 years) were studied initially without any sex steroid replacement (control studies), then on the last day of a 21-day course of oral estradiol-valeriate (E2) administration (2 mg daily) and finally, on the last day of a 21-day course of oral estradiol-progesterone (E2/P4) replacement (2 mg E2 and 200 mg micronized P4 daily). During all study occasions, blood was sampled at 10 min intervals for 10 h, while TRH (200 micrograms iv) was administered 8 h after initiation of blood collections. Compared to the control conditions, serum E2 and P4 concentrations markedly increased (p less than 0.001) following oral E2 or E2/P4 treatments. Total triiodothyronine (T3) and thyroxine (T4) concentrations and free T3 and T4 equivalents remained unchanged during E2 and E2/P4 regimens. In the unstimulated secretory profiles, TSH was found to be episodically released, with little interindividual variability for each study condition. Since the TSH pulse attributes (pulse amplitudes, frequencies, interpulse intervals, mean TSH concentrations, by Cluster pulse algorithm) did not significantly change during E2 and E2/P4 replacements, the episodic character of TSH secretion virtually remained unchanged by sex steroid replacements.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1992

Regulation of adrenal steroidogenesis by adrenaline: expression of cytochrome P450 genes.

The effect of adrenaline on the secretion of cortisol and cyclic AMP (cAMP) and on the accumulation of four different mRNAs encoding cholesterol side-chain cleavage cytochrome P450 (P450scc), 17 alpha-hydroxylase cytochrome P450 (P450(17 alpha)), 21-hydroxylase cytochrome P450 (P450c21) and 11 beta-hydroxylase cytochrome P450 (P450(11 beta)) was studied in bovine adrenocortical cells in primary culture and compared with the effects of ACTH. Treatment of cultured cells with adrenaline (1-100 mumol/l) showed a biphasic response in cortisol release over 1-24 h. Concentration of cAMP in the culture media increased from a basal level of < 0.06 pmol/dish to a maximal level of 40.14 +/- 8.9 pmol/dish with a half-maximal release of 20.07 pmol cAMP/dish in the medium reached 1.2 h after treatment with 10 mumol adrenaline/l. This stimulation resulted in an uniform increase in the levels of all four P450 mRNAs as revealed by Northern blot analysis. Increasing doses of adrenaline produced a maximal mRNA accumulation at a concentration of 10 mumol adrenaline/l. Incubation of the cells with 10 mumol adrenaline/l for 1-24 h produced a biphasic time-course with a half-maximal stimulation after about 5-6 h. Maximal stimulation with ACTH (100 nmol/l) caused different accumulations of the four mRNAs: P450sec mRNA increased twice as much and P450(17 alpha) mRNA six times as much as the accumulation of P450c21 mRNA and P450(11 beta) mRNA, which was about ten-fold over basal values. Propranolol totally blocked the stimulatory effect of adrenaline but not the effect of ACTH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗
PubMed1991

Morphological evidence for a close interaction of chromaffin cells with cortical cells within the adrenal gland.

The adrenal medulla appears to exert a regulatory influence on adrenocortical steroidogenesis. We have therefore studied the morphology of rat, porcine and bovine adrenals in order to characterize the contact zones of adrenomedullary and adrenocortical tissues. The distribution of chromaffin cells located within the adrenal cortex and of cortical cells located within the adrenal medulla was investigated. Chromaffin cells were characterized by immunostaining for synaptophysin and chromogranin A, both being considered specific for neuroendocrine cells. Cortical cells were characterized by immunostaining for 17 alpha-hydroxylase, an enzyme of the steroid pathway. Cellular contacts of chromaffin cells and cortical cells were examined at the electron microscopical level. In rat and porcine adrenals, rays of chromaffin cells, small cell clusters and single chromaffin cells or small invaginations from the medulla could be detected in all three zones of the cortex. Chromaffin cells often spread in the subcapsular space of the zona glomerulosa. In porcine and bovine adrenals, 17 alpha-hydroxylase immunoreactive cells were localized within the medulla. Single cortical cells and small accumulations of cells were spread throughout this region. At the ultrastructural level, the chromaffin cells located within the cortex in pig and rat adrenals formed close cellular contacts with cortical cells in all three zones. Our morphological data provide evidence for a possible paracrine role of chromaffin cells; this may be important for the neuroregulation of the adrenal cortex.

Adrenal Cortex↗