Effect of intraperitoneal administration of bacterial lipopolysaccharide on synthesis of pro-opiomelanocortin mRNA in rat tanycytes.

Intensity of pro-opiomelanocortin mRNA synthesis in tanycytes of adrenalectomied and sham-operated rats was studied by in situ hybridization 4 h after intraperitoneal injection of bacterial LPS. The results were compared with pro-opiomelanocortin mRNA expression in rats subjected to immobilization stress. Immobilization and LPS injection to adrenalectomied and sham-operated animals sharply reduced pro-opiomelanocortin mRNA expression in tanycytes. Injection of LPS to sham-operated animals and immobilization stress caused a significant increase in blood corticosterone level. On the other hand, LPS injection did not change low blood level of corticosterone in adrenalectomied rats. The data indicate a synergic inhibitory effect of glucocorticoids and LPS on synthetic activity of tanycytes.

[Experience with pioglitasone (actos) in the treatment of polycystic ovary syndrome].

The paper presents the authors 'data obtained from examinations of 1 7 patients aged 15 to 36 years who had polycystic ovary syndrome (PCOS) and insulin resistance before and after therapy with pioglitasone in a daily dose of 30 mg, regardless of the time of a meal, for 3 months. The study was undertaken to examine the effects of pioglitasone on carbohydrate and lipid metabolic parameters, as well as on the hormonal parameters of ovarian function and on the basic clinical manifestations in patients with PCOS. Elimination of insulin resistance with the sensitizers of the action of insulin, such as pioglitasone, contributes to the normalization of reproductive function in most patients with PCOS and insulin resistance.

The rat dorsal vagal nucleus: features of cellular and synaptic structure.

Using the stereological, histochemical and electron microscopic approaches the cellular and synaptic structure of the rat dorsal vagal nucleus (DVN) were studied. Cellular organization of the DVN does not allow to distinguish any separate subnuclei but a conspicuous population of mainly small neurons in rostral extension of its lateral part lacking AChE activity. DVN neurons with high and moderate AChE activities are manifest on the 5th postnatal day. Their number increases on the 7th day. In this critical period of the brain sexual differentiation, a sexual dimorphism was observed in the activity of DVN cholinergic neurons. The electron microscopic studies showed a wide variety of the DVN synaptic patterns. In the rat DVN were found complicated synaptic structures resembling glomeruli. Two types of synaptic glomeruli are distinguished. The results suggest that DVN can be regarded as a sex-dependent brain area involved in a high level of information processing.

Role of hypothalamic circuitries in neuroendocrine regulations: hypothalamus - endocrine pancreas interactions, a new concept.

Though there is no lack in proofs of hypothalamic involvement in regulating endocrine pancreas and related aspects of metabolism, the mechanisms thereof are still pending elucidation. There is no adequate tropic hormone in the anterior pituitary hence the conventional hypothalamic-hypophyseal route may only function as circuitous. This lends special appeal to a probable hypothalamic participation over purely neural route, one implicated in insulin secretion, for example via the vagus. This has long been considered possible but has not been explored. Summed up are results of many years of experimental research by the author and his group in hypothalamic-vagal neural connections. The following techniques were employed: karyometric and relevant histochemical studies of rat medullary vagal nuclei and hypothalamic nuclei under insulin deficiency; karyometric studies of transneuronal changes in dorsal vagal nuclei, as well as silver impregnation studies of preterminal axons and their terminal branches (Fink-Heimer technique) for degeneration together with ultrastructural studies of presynaptic profile degeneration in dorsal vagal nuclei of rats bearing electrolytic lesions placed in the hypothalamic areas, in which descending axons are presumed to originate. The results obtained indicate there exists a direct hypothalamic-vagal descending pathway, which originates in paraventricular nuclei and synapses on neurons of the dorsal vagal nuclei after partial crossing over in the lower brain stem. Possible mechanisms at hypothalamic and medullary levels in neuroendocrine regulations of pancreatic islets are discussed.

The origin of the hypothalamic-vagal descending pathway: an experimental ultrastructural study.

Placing uni- and bilateral electrolytic lesions in the rat hypothalamic paraventricular nuclei was followed by the degradation of presynaptic profiles in the medullary dorsal vagal nuclei. Unilateral lesions resulted in degeneration of the dorsal vagal nuclei presynaptic profiles on the side of the lesion and on the site opposite. Our results seem to afford the first experimental proof that descending hypothalamic axons synapsing in the medulla on the neurons of the dorsal vagal nuclei arise in the paraventricular nuclei and intersect at some level of the lower brain stem.

Tanycytes and their relation to the hypophyseal gonadotrophic function.

It is shown by the enzyme-histochemical method that after prenatal androgenization (the administration of 25 mg testosterone propionate to the mother on the 19th day of pregnancy) female rats lose the sex differences in the age dynamics of the activity of some dehydrogenases in the beta 1-tanycytes, which were detected earlier in the 'critical period'. The data of the present study are regarded as further evidence in favor of the earlier advanced assumption of beta 1-tanycyte hypersensitivity to the sex hormones. The authors develop an original hypothesis on the possible role of beta 1-tanycytes in the feedback control of gonadoliberin release from the nerve terminals of the median eminence.

Ultrastructural evidence for the existence of a direct hypothalamic--vagal descending pathway.

The ultrastructural changes in the presynaptic nerve terminals in the dorsal vagal nucleus were studied in rats with bilateral electrolytic lesions placed in the dorso-medio-caudal hypothalamic area in the sagittal plane of the dorsomedial nuclei, just behind these nuclei in the P3,5--P3,7 interval. On days 3, 4 and 5 following placement of the hypothalamic lesions, degeneration of some of the presynaptic profiles in the dorsal vagal nucleus was found in the experimental animals. The data obtained provide evidence for the existence of descending hypothalamic axons terminating in the medulla oblongata on the neurons of the dorsal vagal nucleus. The possible involvement of the descending hypothalamic--vagal nerve pathway in the control of endocrine pancreas is discussed.

[Ultrastructural characteristics of the specialized ependyma of the 3d cerebral ventricle in rats]. / Ul'trastrukturnaia kharakteristika spetsializirovannoi épendimy 3-go zheludochka mozga u krys.

The ultrastructure of the specialized ependyma of the third cerebrals ventricle was studied in males of albino Wistar rats, 160--180 g of weight. The ependyma lining the inferolateral walls (alpha-tanycytes) was found to differ ultrastructurally from that of the floor of the third ventricle or of the median eminence (beta-tanycytes). These differences are assumed to reflect a specific functional differentiation of the different types of tanycytes. Various types of microvesicles and a system of peculiar membranous cavities are described in the alpha-and beta-tanycytes. These structures are supposed to be associated with the transport and secretory function of tanycytes.

CNS--endocrine pancreas system. III. Further studies on the vagal responsiveness to insulin deficiency.

Distribution and activity of acetylcholinesterase (AChE) in the neurons of the central vagal nuclei at the level of the medulla oblongata were studied in intact and alloxan-diabetic adult male rats by Gomori's histochemical method. Peculiarities of intracellular distribution of the enzyme in the Nucl. dorsalis n. vagi (ND) and Nucl. ambiguus n. vagi (NA) of intact animals were demonstrated. Changes in the ratio of cholinergic neurons with moderate and strongly-positive AChE staining reactions were revealed in the ND of alloxan-diabetic rats. The dynamics of the changes attested to increased AChE activity of these neurons in response to insulin deficiency. The data obtained are additional evidence for the responsiveness of ND neurons to insulin deficiency, which was demonstrated earlier in alloxan-diabetic rats by karyometry (Akmayev and Rabkina, 1976 b). It is suggested that changes in the plasma glucose or insulin levels may be the stimulus that influences the activity of the ND cholinergic neurons. By means of this mechanism the central vagal nucleus at the medulla oblongata level may be implicated in the feedback control of insulin secretion.

Morphological aspects of the hypothalamic-hypophyseal system. VII. The tanycytes: Their relation to the hypophyseal adrenocorticotrophic function. An ultrastructural study.

The ultrastruct of the tanycyte ependyma in male 160-180 g Wistar albino rats was studied under normal conditions and in experiments involving long-term suppression of ACTH secretion and its long-term stimulation. The former was accomplished by daily (for 8 days) intraperitoneal administration of dexamethasone phosphate at low (5 microgram/100 g) and high (100 microgram/100 g) concentrations. The effectiveness of suppression of the hypothalamic-hypophyseal-adrenal system in the experimental animals was judged by their reaction to two-minute ether stress (determination of plasma corticosterone) and by the results of measurement of the adrenal weights. Stimulation of ACTH secretion was achieved by bilateral adrenalectomy; the animals were examined on days 8, 10, 14, and 22 following the operation. The results obtained were in agreement with the previously established fact that there is a negative correlation between tanycyte activity and hypophyseal adrenocorticotropic function (Akmayed and Fidelina, 1974). They also testified to the predominant involvement of the median eminence tanycyte ependyma (beta-tanycytes according to the author's nomenclature) in these relationships. It is supposed that correlations are regulated by a feedback mechanism and attest to the involvement of beta-tanycytes in the inhibiting control of hypophyseal adrenocorticotrophic function. The mechanism of this control may be explained alternatively: either the tanycytes transport ACTH-suppression substances (catecholamines, corticosteroids, ACTH) from the CSF to the hypophyseal portal system or they themselves secrete substances possessing ACTH-suppressive activity. The authors distinguish several types of vesicles in the beta-tanycytes, the number of which changed with experimentally induced shifts in hypophyseal adrenocorticotrophic function. These vesicles are discussed in connection with the transport and secretory activity of the tanycytes and are considered to be a possible substrate of the hypothalamic inhibiting effect on ACTH secretion.

Morphological aspects of the hypothalamic-hypophyseal system. VI. The tanycytes: their relation to the sexual differentiation of the hypothalamus. An enzyme-histochemical study.

Enzyme-histochemical methods were used to study the metabolic activity of specialized ependyma of the ventrolateral walls and floor of the third ventricle in young male and female rats during the "critical period" of sexual differentiation of the hypothalamus (one week after birth). Histochemical tests were conducted for glutamic dehydrogenase, lactic dehydrogenase, glucose-6-phosphate dehydrogenase, glycerophosphate dehydrogenase and NADH2-dehydrogenase. Enzyme activity was judged by cytospectrophotometry. All the data were treated statistically. It was found that the specialized ependyma of the ventrolateral wall and floor of the third ventricle (median eminence) in rats differed in their enzyme behaviour in males and females during the "critical period" of sexual differentiation of the hypothalamus. At the level of the arcuate nucleus (alpha2-tanycytes) and the medial part of the median eminence (beta2-tanycytes) the ependyma was characterized by similar indices of metabolic activity in males and females in the decisive terms of the "critical period" (days 3, 5, and 7). On day 5 metabolic activity of these cells was reduced both in the males and in the females. Prominent sexual differences in the intensity of the enzyme reactions studied were noted in the ependyma of the lateral parts of the median eminence (beta1-tanycytes) in the "critical period". On day 5 metabolic activity of beta1-tanycytes was reduced in males and increased in females. It is suggested that these differences are caused by the receptor nature of beta1 tanycytes and suggest their implication in the mechanisms of sexual differentiation of hypothalamus.

CNS-endocrine pancreas system. I. The hypothalamus response to insulin deficiency.

The anterior, medial and posterior hypothalamic nuclei in alloxan-diabetic male rats were studied by karyometry. Selective responsiveness of separate nuclei of the medial basal hypothalamus (MBH) and the anterior hypothalamus was revealed. In the MBH cell nuclear-size changes were most prominent in the ventromedial nucleus and less pronounced, but significant, in the arcuate nucleus. In the anterior hypothalamus a significant response was produced by the supraoptic nucleus. The authors do not exclude the possibility that the reaction of the neurosecretory cells of the supraotic nucleus is indirect and reflects disturbed vasopressin balance in alloxan-diabetic rats in response to impairment of water-salt metabolism. The responsiveness of the MBH nuclei is considered as evidence for their involvement, the bentromedial nucleus in particular, in hypothalamic control of the endocrine pancreas. Various means by which insulin-sensitive hypothalamic areas may be implicated in this control are discussed.

CNS-endocrine pancreas system. II. Response of dorsal nucleus of the vagus nerves to insulin deficiency.

Sensitivity of the vagal dorsal nucleus nerve cells to insulin deficiency was revealed in alloxan-diabetic rats by karyometry. Control measurements showed absence of similar changes in cell nuclear sizes of the adjoining area, the Nucltractus solitarii. The results provide evidence in favour of a selective response of the dorsal nucleus of the vagus nerves to insulin deficiency and allow assumption that not only the peripheral vagus but the central component of this cholinergic system contribute to endocrine pancreas control. It is suggested that the medial basal hypothalamus and the system of the vagus are links of a single control mechanism regulating endocrine pancreas and represented at different levels of the central and peripheral nervous system.