Monika Ehrhart-Bornstein

Role of the Vasoactive Intestinal Peptide in a Neuroendocrine Regulation of the Adrenal Cortex

Using a method for isolation and perfusion of pig adrenal glands with preserved nerve supply, we measured the release of cortisol and aldosterone and of the vasoactive intestinal peptide (VIP) after electrical stimulation of the splanchnic nerves. Additionally, the effect of VIP (at final concentrations of 10(-10)-10(-7) M) in the perfusion medium on the release of cortisol and aldosterone was investigated. The amount of VIP contained within the adrenal was measured by chromatography, and the localization of VIP in the adrenal gland was investigated immunohistochemically. Stimulation of the splanchnic nerves provoked a significant release of VIP (2.7- to 17-fold) and of the corticosteroids cortisol (2.5- to 6.7-fold) and aldosterone (1.6- to 2.8-fold). VIP added to the perfusion medium stimulated secretion of both corticosteroids with a maximal effect at 10(-8) M. Cortisol release increased 20- to 58.5-fold over basal, aldosterone release increased 2.9- to 4.9-fold over basal. This VIP-stimulated release had the same range of magnitude as the release stimulated by adrenocorticotropic hormone in physiological concentrations (10(-10) M). The mean concentration of VIP-like immunoreactivity in the adrenal glands was 8.9 +/- 2.1 pmol/g wet weight. Immunohistochemical investigations showed immunoreactive cells within the adrenal medulla as well as VIP-ergic nerve fibers in the cortex of the adrenal gland. These data show that the adrenal cortex can be stimulated independent of the hypothalamus-pituitary-adrenal axis via a neuroadrenocortical axis. In this regulatory pathway, the VIP-ergic innervation of the adrenal cortex may be a potent stimulatory element.

Parallel expression of synaptophysin and evoked neurotransmitter release during development of cultured neurons

Primary cultures of GABAergic cerebral cortex neurons and glutamatergic cerebellar granule cells were used to study the expression of synaptophysin, a synaptic vesicle marker protein, along with the ability of each cell type to release neurotransmitter upon stimulation. The synaptophysin expression and neurotransmitter release were measured in each of the culture types as a function of development for up to 8 days in vitro, using the same batch of cells for both sets of measurements to obtain optimal comparisons. The content and the distribution of synaptophysin in the developing cells were assessed by quantitative immunoblotting and light microscope immunocytochemistry, respectively. In both cell types, a close parallelism was found between the temporal pattern of development in synaptophysin expression and neurotransmitter release. This temporal pattern differed between the two types of neurons. The cerebral cortex neurons showed a biphasic time course of increase in synaptophysin content, paralleled by a biphasic pattern of development in their ability to release [3H]GABA in response to depolarization by glutamate or elevated K+ concentrations. In contrast, a monophasic, approximately linear increase in the synaptophysin content and stimulated [3H]D‐aspartate release was found in the cerebellar granule cells. These results, particularly regarding the GABAergic neurons, offer correlative evidence in support of the notion that a vesicular pool of these amino acid neurotransmitters may be intimately involved in their release, subsequent to depolarization stimuli.

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.

Chronic osmotic stimulation reduces vasopressin but not synaptophysin content in rat neurohypophysis.

The content of synaptophysin, a vesicular integral membrane protein of neurons and endocrine cells, and that of vasopressin was measured in neurohypophyses of rats during chronic osmotic stimulation. The animals received 2% NaCl in their drinking water for up to 4 days. Synaptophysin content of neurohypophyses was determined using quantitative immunoblotting, vasopressin content was measured by radioimmunoassay. Salt loading caused a decrease in the content of vasopressin to about 15% of that of control animals, whether expressed per neurohypophysis or relative to the total tissue protein. In contrast, no change was found in the synaptophysin content. Taken together with published evidence of changes in the relative numbers of the hormone-containing neurosecretory granules (NSGs) and the microvesicles (MVs) under the conditions of chronic osmotic stimulation, these results strongly indicate the surface density of synaptophysin on NSGs to be significantly lower than its surface density on MVs.

Stem Cell Growth as a Model of Carcinogenesis

Steven Poser1, Joseph Alisky2, Kuei-Fang Chung3, Doreen Ebermann3, Monika Ehrhart-Bornstein3, Stefan Bornstein3 and Andreas Androutsellis-Theotokis3,4,5 1Celling Technologies, Austin, Texas, 2Total Longterm Care, Aurora, Colorado, 3Carl Gustav Carus University Medical School, Medical Clinic III, Dresden University of Technology, Dresden, 4Center for Regenerative Therapies, Dresden University of Technology, Dresden, 5European Brain Research Institute, Rome, 1,2USA 3,4Germany 5Italy

Regulation of Adrenocortical Function by the Sympathoadrenal System

In the first complete description of the adrenal gland in 1852, von Kolliker described the adrenal as composed of two different tissues, with the cortex belonging to the “blood-vascular glands” and the medulla, a part of the nervous system, resembling a ganglion (1). The astonishing arrangement of these two tissues justifies the question: What is a ganglion doing inside a gland (2)?