Arginine vasopressin (AVP): a review of its historical perspectives, current research and multifunctional role in the hypothalamo-hypophysial system.

INTRODUCTION: This publication reviews the function of arginine vasopressin and focuses on the morphologic and functional correlation between the hormone and its effect on stress, the hypophysial-adrenocortical axis, neuroimmune responses, renal function and corticotroph pituitary tumors. MATERIALS AND METHODS: A literature review was performed using various search engines for information regarding the morphology and the multifunctional role of arginine vasopressin. RESULTS: Although a large number of studies were published discussing these interactions, there are several important areas that are still obscure. CONCLUSION: The questions of how does arginine vasopressin affect the morphology and function of these various areas, and how does the secretion of ACTH and adrenocortical hormones influence the morphology of arginine vasopressin-producing cells and their hormone secretion requires further investigation.

Effects of neurointermediate pituitary lobectomy and desmopressin on acute experimental autoimmune encephalomyelitis in Lewis rats.

OBJECTIVE: The role of arginine vasopressin (AVP) as a direct immune regulator has not yet been clarified, and more work is needed to assess its involvement in the immunoneuroendocrine network. In the present study, the effects of neurointermediate pituitary lobectomy (NIL) and desmopressin (DP), an agonist of AVP, on acute experimental autoimmune encephalomyelitis (EAE) in female Lewis rats were evaluated. The activity of the hypothalamic-pituitary-adrenocortical (HPA) axis was also assessed. METHODS: Five groups of rats were used, as follows: (1) sham-operated (SHAM) rats, (2) SHAM + DP rats, (3) NIL rats, (4) NIL + DP rats and (5) untreated normal control rats. DP treatment started 2 weeks after surgery, and immunization to induce EAE was carried out 1 week later. RESULTS: SHAM rats developed full-blown clinical and histological signs of EAE and activation of the HPA axis. SHAM + DP animals had mild clinical signs of EAE, inflammatory infiltrations in the spinal cord and an activated HPA axis. NIL animals developed minimal EAE, scanty spinal cord inflammation and no changes in HPA axis activity. NIL + DP rats developed severe clinical signs of EAE, extensive spinal cord inflammatory infiltrations and marked activation of the HPA axis. CONCLUSIONS: NIL decreased the cell-mediated immune response, while DP in NIL animals restored the immune response. AVP is directly involved in the maintenance of immune competence.

Adenohypophysitis in rat pituitary allografts.

The histological, immunohistochemical and ultrastructural alterations in 81 pituitary allografts from Lewis rats transplanted beneath the renal capsule of Wistar rats were investigated. Intrasellar pituitaries of rats bearing allografts were also examined. Recipient rats were sacrificed at various time points after transplantation. Two days after transplantation, the central portion of the allografts demonstrated ischaemic necrosis. A week later, massive mononuclear cell infiltrates consisting primarily of lymphocytes and to a lesser extent, macrophages, plasma cells and granulocytes became prominent. At about three to four weeks after transplantation, the mononuclear cell infiltrate diminished; the surviving adenohypophysial cells, mainly prolactin (PRL) cells, increased in number and necrosis was replaced by connective tissue. No histological changes were noted in the intrasellar pituitaries of rats bearing allografts. Immunohistochemistry demonstrated that the surviving adenohypophysial cells were mainly PRL-producing cells. Electron microscopy revealed adenohypophysial cell destruction, a spectrum of inflammatory cells and, in late phase, accumulation of fibroblasts and collagen fibres. PRL cells were the prominent cell types; they increased in number. It appears that pituitary allografts are 'foreign' and evoke an immune response, suggesting that they may be used as an experimental animal model for morphological investigation of the development and progression of adenohypophysitis, a rare disease occurring mainly in young women often associated with pregnancy.

Synthesis and evaluation of estrogen agonism of diaryl 4,5-dihydroisoxazoles, 3-hydroxyketones, 3-methoxyketones, and 1,3-diketones: a compound set forming a 4D molecular library.

In this paper, the preparation and systematic evaluation of estrogen receptor alpha (ER alpha) and estrogen receptor beta (ER beta) activities of some diaryl-1,3-diones and their synthetic intermediates, diaryl-4,5-dihydroisoxazoles, diaryl-3-hydroxyketones, diaryl-3-methoxyketones, and diaryl-2-(dimethyl-lambda 4-sulfanylidene)-1,3-diones, is described. The set of 72 compounds constitutes a general schematic structure aryl1-linker1-spacer-linker2-aryl2, where the linker1-spacer-linker2 length varies between 4 and 8 carbons. The set of compounds was applied here to map and explore the active sites of subtypes ER alpha and ER beta. The highest activities were obtained with dihydroisoxazole and hydroxyketone spacers, but even the most flexible diones with unsubstituted aryl groups showed some agonism. Most compounds were found to be ER alpha selective or to activate both receptors, but in some cases we saw also clearly stronger ER beta activation.

Neurointermediate pituitary lobectomy decreases the incidence and severity of experimental autoimmune encephalomyelitis in Lewis rats.

Acute experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the central nervous system, mediated by T lymphocytes. Immunization of Lewis rats with myelin antigens suspended in complete Freund's adjuvant induces EAE. In a previous study on rats we have found that neurointermediate pituitary lobectomy (NIL) decreased both the humoral and cell-mediated immune responses. Here we investigated the effect of NIL on the incidence and severity of EAE and on the function of the hypothalamic-pituitary-adrenal axis in Lewis rats. NIL, hypophysectomized (Hypox) and sham-operated (Sham) rats were immunized s.c. with guinea-pig brain extract suspended in complete Freund's adjuvant. Untreated rats were used as controls. Water intake, body weight gain, clinical and histopathologic incidence and severity of EAE were evaluated in the operated groups. On killing, plasma adrenocorticotropin and corticosterone levels were measured and adrenals, thymuses and spleens were weighed. Histopathologic lesions were counted in the brain and spinal cord. Water intake and body weight gain were significantly decreased in Sham and Hypox animals with EAE whereas higher intakes persisted in the NIL group. Plasma levels of adrenocorticotropin were within the normal range whereas corticosterone levels increased in Sham and occasionally in NIL animals. Thymus weights were decreased in NIL and Hypox groups. The clinical and histopathologic incidence and severity of EAE were significantly decreased in NIL animals as compared with Sham and Hypox rats. We concluded that NIL affects the cell-mediated immune response and plays a role in the development and progression of EAE in the Lewis rat.

Regulation of intestinal morphology and GALT by pituitary hormones in the rat.

Here, the effects of neurointermediate (NIL), anterior (AL), and total hypophysectomy (HYPOX) on ileal mucosa cells and gut-associated lymphoid tissue (GALT) are reported. Compared with the sham-operated (SHAM) rats, the villi height and goblet cells numbers were significantly decreased in all groups. Lamina propria area decreased in AL and HYPOX, but not in NIL animals. CD8(+) but not CD4(+) lymphocytes decreased in the HYPOX and NIL groups. Paneth cells did not change, while IgA cells, IgM cells, and secretory IgA were significantly decreased in all groups. NIL but not AL animals lost significant numbers of IgA cells and secretory IgA. In summary, pituitary hormones exert lobe-specific regulatory effects on the gut and on GALT.

Neuroimmune regulation in immunocompetence, acute illness, and healing.

Adaptive immunocompetence is maintained by growth hormone (GH), prolactin (PRL), and vasopressin (VP). Innate or natural immunocompetence depends on cytokines, hormones (especially of the hypothalamus-pituitary-adrenal axis), and catecholamines. The acute phase response (APR, or acute febrile illness) is an emergency defense reaction whereby the adaptive, T cell-dependent, immune reactions are suppressed and the innate immune function is dramatically amplified. Infection and various forms of injury induce APR. Cytokines [interleukin (IL)-1beta, tumor necrosis factor-alpha, and IL-6] stimulate corticotropin-releasing hormone (CRH) and VP secretion and cause a "sympathetic outflow." Colony-stimulating factors activate leukocytes. CRH is a powerful activator of the pituitary adrenocortical axis and elevates glucocorticoid (GC) levels. Cytokines, GCs, and catecholamines play fundamental roles in the amplification of natural immune defense mechanisms. VP supports the APR at this stage. However, VP remains active and is elevated for a longer period than is CRH. VP, but not CRH, is elevated during chronic inflammatory diseases. VP controls adaptive immune function and stimulates adrenocorticotropic hormone (ACTH) and PRL secretion. PRL maintains the function of the thymus and of the T cell-dependent adaptive immune system. The ACTH-adrenal axis stimulates natural immunity and of suppressor/regulatory T cells, which suppress the adaptive immune system. VP also has a direct effect on lymphoid cells, the significance of which remains to be elucidated. It is suggested that VP regulates the process of recovery from acute illness.

Hypophysectomy and neurointermediate pituitary lobectomy reduce serum immunoglobulin M (IgM) and IgG and intestinal IgA responses to Salmonella enterica serovar Typhimurium infection in rats.

The influence of anterior pituitary hormones on the gastrointestinal tract of humans and animals has been reported. Hypophysectomy (HYPOX) in the rat causes atrophy of the intestinal mucosa, reduction of gastric secretion and intestinal absorption, and increased susceptibility to infections. To our knowledge, there are no studies on the humoral immune response of the gut-associated lymphoid tissue after HYPOX. We have reported that decreased secretion of vasopressin and oxytocin due to neurointermediate pituitary lobectomy (NIL) diminishes humoral and cell-mediated immune responses. However, no data have been published on whether NIL can affect intestinal immune responses. We analyzed the effects of HYPOX and NIL on bacterial colonization of the intestinal lumen, Peyer's patches, and spleen as well as the serum immunoglobulin G (IgG) and IgM and specific intestinal IgA levels in response to Salmonella enterica serovar Typhimurium oral infection. Results showed the following: (i) Salmonella serovar Typhimurium was eliminated from the intestinal lumen at the same rate in rats that underwent a sham operation, HYPOX, and NIL; (ii) Salmonella serovar Typhimurium colonization of Peyer's patches and spleen was significantly higher in both HYPOX and NIL rats than in sham-operated rats; (iii) serum IgG and IgM and intestinal IgA against surface proteins of Salmonella serovar Typhimurium were significantly lower in HYPOX and NIL rats than in sham-operated rats; and (iv) compared to NIL rats, higher Peyer's patch and spleen bacterial colonization and decreased IgG, IgM, and IgA production were observed in HYPOX rats. We conclude that hormones from each pituitary lobe affect the systemic and gastrointestinal humoral immune responses through different mechanisms.

The role of prolactin in the pathogenesis of autoimmune disease.

Prolactin has emerged in recent years as a major regulator of both the maturation and the function of lymphocytes. Prolactin abnormalities, which include elevated serum levels, decreased bioactivity, abnormal circadian rhythm, and exaggerated secretion after stimulation by TRH, are associated with various autoimmune conditions in humans. Some animal experiments and observations in humans indicate that proiactin has an important role in the pathogenesis of autoimmune disease. There are several mechanisms through which prolactin could promote the development of autoimmunity. It is concluded that prolactin abnormalities alone are not likely to cause autoimmunity, but rather additional regulatory defects are perhaps also required for disease to develop.

Effects of neurointermediate pituitary lobectomy on humoral and cell-mediated immune responses in the rat.

OBJECTIVE: Chronic stress is characterized by an increased activity of the hypothalamic-pituitary-adrenocortical axis and decreased humoral and cell-mediated immune responses. In the rat, corticosterone is the principal natural immune suppressor. Neurointermediate pituitary lobectomy (NIL) in rats induces diabetes insipidus and protracted increases in basal adrenocorticotropin and corticosterone plasma levels, a situation that resembles chronic stress. In this paper, we evaluated the effects of NIL on humoral (hemagglutinin titers and footpad swelling to sheep red blood cells--SRBC) and cell-mediated immune responses (contact hypersensitivity to dinitrochlorobenzene). METHODS: The studies were conducted on NIL Wistar rats (body weight 150-200 g) 3 weeks after surgery. For comparisons, nonoperated control rats were used. RESULTS: NIL resulted in an increased water intake. Body weight gain and adrenal, thymus, and spleen weights were within the range of nonoperated controls. Eight days after SRBC immunizations a second SRBC injection into the footpad resulted in a decreased swelling response in NIL rats. The hemagglutinin titers were also reduced in the NIL rats. CONCLUSIONS: These results indicate that: (1) NIL reduces humoral immune responses and decreases the cell-mediated immune response; (2) the immune alterations are most likely due to the increased activity of the hypothalamic-pituitary-adrenocortical axis induced by NIL, and (3) NIL animals constitute a valuable paradigm to study hypothalamic-pituitary-immune interactions.