Posterior Lobe Hormones Research Articles

Establishment and Application of an Index System for the Risk of Drug Shortages in China: Based on Delphi Method and Analytic Hierarchy Process.

At present, the avoidance of drug shortages mainly relies on expert experience. This study aimed to establish an evaluation index system for the risk of drug shortages in medical institutions in China and to apply the system to guide the graded management of drugs in short supply. A two-round Delphi process was conducted to determine the indicators in the index system. The weight value of each indicator was calculated using analytic hierarchy process (AHP) methods. The data of drugs in short supply from January 1 to December 31, 2020 in Hunan province were collected and evaluated using this index system. The evaluation scores, which ranged from 0 to 100, were calculated. A three-level index system with four first-level indicators, 11 second-level indicators, and 36 third-level indicators was constructed by the two rounds of the Delphi process. The expert authority coefficient (Cr) of the first and second rounds of consultation were 0.88 and 0.90, respectively. The Kendall's coefficients of concordance (Kendall's W) for the two rounds of consultation were 0.44 and 0.50, respectively (P<.05). For the first-level indicators 'supply stability,' 'causes of shortage,' 'medicine availability in medical institution' and 'pharmaceutical properties,' the weight values were 0.3253, 0.2489, 0.2398, and 0.1860, respectively. Based on the risk evaluation score, drugs (dosage strength) at high risk of shortage included sodium thiosulfate (0.64 g), posterior pituitary lobe hormones (1 mL:6 IU), protamine sulfate (5 mL:50 mg), thrombin (500 U), urokinase (10 WU), and rotundine sulfate (2 mL:60 mg). An indexed system for the risk assessment of drug shortages in China was established to guide the graded response to drug shortages in medical institutions and the implementation of differential management strategies to address these shortages.

Androgen‐binding Protein is Co‐Expressed with Oxytocin in the Male Reproductive Tract

Androgen-binding protein (ABP) and the posterior lobe hormone oxytocin (OT) were co-localized in male rat reproductive organs. Immunostaining of serial semi-thin sections revealed a high rate of coexistence of both antigens in Sertoli cells and in the epithelial cells of the prostate. There was a considerably less co-localization of OT and ABP in epithelial cells of the epididymis, and in the different tissues of the ductus deferens. In situ hybridization with synthetic oligonucleotides complementary to a fragment of ABP mRNA showed specific staining in the same sites that were immunostained for ABP. ABP was isolated by affinity chromatography from homogenates of testis, epididymis, prostate and the content of the prostate lumen. Identical protein patterns could be shown with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry in all samples except for the epididymis indicating that ABP structure is similar in all these tissues. ABP seems to be expressed in specified cells throughout the male rat reproductive tract. Most of these cells appear to be oxytocinergic. ABP and OT have previously been detected in the ejaculate. The observed epithelial cells are likely to be their source.

Diabetes Insipidus: Historical Aspects

The contributions to our present knowledge and understanding of diabetes insipidus are briefly surveyed. Though a disease presenting with polyuria and thirst had been recognized since Antiquity, it was not until the 17. Century the distinction was made between diabetes insipidus and diabetes mellitus. At the beginning of the 20. Century almost nothing was known about the function of the pituitary. It was generally believed that diabetes insipidus was a renal disease. Two clinical observations in 1912 suggested an association between the hypophysis and diabetes insipidus. This view was supported by the recognition in 1913 that extract of the posterior lobe of the pituitary was effective in diabetes insipidus. Despite much evidence to the contrary, it was assumed that the antidiuretic hormone was produced in the intermediate lobe of the pituitary. Around 1950 it was finally established that 'the posterior lobe hormones' are in fact secreted in the hypothalamus. At the same time the antidiuretic hormone was isolated and synthesized. More recently, progress within genetics has made it possible to characterize in details other rare types of diabetes insipidus.

Colocalization of vasopressin and oxytocin in hypothalamic magnocellular neurons in water-deprived rats

The posterior lobe hormones vasopressin and oxytocin are expressed in mutually-exclusive sets of magnocellular hypothamalic neurons. However, under certain functional conditions a partial coexpression has been observed. In the present study we subjected adult rats to long-term osmotic stress by water deprivation for up to 3 days.After 3 days, a marked reduction of vasopressin immunostaining was observed in the paraventricular and supraoptic nuclei as compared with controls. Coexistence of oxytocin and vasopressin occurred in a portion of the magnocellular neurons. Many fibers of the hypothalamic-neurohypophyseal tract contained both peptides. Rehydration for 24 h after 3 days of thirsting resulted in a light recovery of vasopressin immunoreactivity with almost none magnocellular neurons containing both nonapeptides. Our findings indicate that magnocellular hypothalamo neurohypophysial neurons are capable of oxytocin and vasopressin coexpression upon extended osmotic stress.

Organisation of basement membrane components in the human adult and fetal pituitary gland and in pituitary adenomas.

Cell-matrix interactions undoubtedly have a role in the development and maintenance of the complex nonrandom structure of the human pituitary gland. We have extended previous studies by documenting the patterns of immunoreactivity for type IV collagen, laminin and fibronectin in the fetal gland, comparing these with the adult patterns. In both we have examined the differences between the anterior lobe and intermediate zone in an attempt to elucidate the apparent differences in functional response between corticotrophs in the two areas. We have also examined expression of these proteins in a series of pituitary adenomas. Finally, we have immunolocalised beta 4 integrin, a component of the alpha 6 beta 4 laminin receptor, in the adult gland and in adenomas. In the anterior lobe of the adult gland, type IV collagen and laminin were present in both epithelial and vascular basement membrane. Fibronectin was related to the basement membrane but showed a less continuous distribution. beta 4 Integrin was expressed on the basal aspects of pituitary cells, in association with laminin, suggesting that this did identify the alpha 6 beta 4 laminin receptor. In addition, immunoreactivity was present on the lateral margins of some pituitary cells, which might indicate a role in cell-cell adhesion. None of the proteins showed specific association with any particular cell type, suggesting that these specific interactions do not regulate differentiation. This pattern of expression had developed in the fetal gland by the second trimester, with expression relating to vessels preceding that in epithelial basement membrane. Type IV collagen, laminin and fibronectin were also expressed in epithelial and vascular basement membrane in the intermediate zone of the adult gland, and around Rathke's cleft in the fetal gland. However, the organisation differed, with larger groups of cells enclosed within a single basement membrane. Possible vascular connections demonstrated between the posterior lobe and the intermediate zone would permit access of posterior lobe hormones to this zone. Our data confirmed disruption of expression in pituitary adenomas, type IV collagen, laminin and beta 4 integrin having a mainly perivascular distribution, with more variable immunoreactivity for fibronectin.

Immunohistochemical studies on the distribution of endogenous digitalis-like substance(EDLS)-containing neurons in the rat hypothalamus, with special consideration on the possibility of their coexistence with posterior lobe hormones.

The distribution of the perikarya of endogenous digitalis-like substance (EDLS)-containing neurons in the rat hypothalamus was studied by immunohistochemistry using digoxin and digitoxin antiserum. In addition, the possible coexistence of EDLS and posterior lobe hormones was examined using an immunohistochemical double-staining technique. Digoxin-like immunoreactive neurons were demonstrated in the paraventricular and supraoptic nuclei and other hypothalamic areas. However, digitoxin-like immunoreactive neurons were not detected in the hypothalamus. A portion of the digoxin-like immunoreactive neurons showed immunoreactivity for vasopressin or oxytocin. From these results, it is suggested that these digoxin-like immunoreactive neurons correspond to "EDLS-producing neurons," and that EDLS seems to act not only as a natriuretic substance but also as a neurohormone or neurotransmitter.

Alpha 1-adrenergic receptors in the neural lobe of the rat pituitary: autoradiographic identification and localization.

alpha 1-Adrenergic receptors were identified, characterized, and localized in rat pituitary gland by quantitative light microscopic autoradiography. Autoradiographic studies were carried out in slide-mounted rat pituitary sections using both [125I]2-[beta-(4-hydroxy-3-iodophenyl)ethyl-aminomethyl]tetralone ([125I]HEAT) and [3H]prazosin to localize alpha 1-adrenergic receptors. Data analysis by densitometry showed that [125I]HEAT binding in the rat neural lobe was saturable and of high affinity, with an apparent dissociation constant (Kd) of about 5 pM. Data from competition studies using a variety of compounds demonstrated an alpha 1-adrenergic receptor profile for [125I]HEAT-binding sites in the rat pituitary. A high density of alpha 1-adrenergic receptors (1 microM prazosin-displaceable [125I]HEAT binding or 10 microM phentolamine-displaceable [3H]prazosin binding) was found present only in the neural lobe, with negligible concentrations in the anterior and intermediate lobes. The regulation of [125I]HEAT-binding sites in the neural lobe was examined in pituitary stalk-transected and superior cervical ganglionectomized rats. Significant increases in [125I]HEAT-binding sites were observed after superior cervical ganglionectomy, but no changes in [125I]HEAT binding were found in pituitary stalk-transected rats compared to that in sham-operated controls. These data provide the first identification of alpha 1-adrenergic receptors in the neural lobe of the rat pituitary and suggest that these receptors may be localized primarily in blood vessels. In addition, a primary role for the peripheral sympathetic nervous system in regulating the neurohypophyseal vasculature is suggested. The precise function of alpha 1-adrenergic receptors in the neural lobe in regulating posterior lobe hormone secretion remains to be demonstrated.

Presence of met-enkephalin in bovine pituitary intraglandular colloid of intermediate lobe origin

Met-enkephalin, and opioid peptide present in the intermediate lobe of the pituitary gland, is herein demonstrated, for the first time, in bovine pituitary intraglandular colloid. Colloid samples were taken from the glands of freshly slaughtered cattle, pooled, lyophilized, extracted on octadecylsilyl-silica and assessed by radioimmunoassay. Met-enkephalin was indeed present in this colloid extract at levels varying from 0.40 to 0.85 nanograms per milligram dry weight. Locating an intermediate lobe peptide in intraglandular colloid is a significant finding since this implies that colloid, housed in the intraglandular lumen, may serve as a transport medium. Intermediate lobe peptides which, because the intermediate lobe is avascular, are otherwise denied the vascular transport routes available to the anterior and posterior lobe hormones.

Differences in the distributional pattern of CRF-, oxytocin-, and vasopressin-immunoreactive nerve fibers in the median eminence of the rat.

Conspicuous differences in the distributional pattern of nerve fibers containing corticotropin-releasing factor (CRF) or posterior lobe hormones, respectively, were shown in the median eminence of the adult male rat by means of immunoperoxidase histochemistry, with the use of anti-CRF, anti-oxytocin, and anti-vasopressin sera. In the rostral and central divisions of the median eminence, a high concentration of CRF-immunoreactive nerve fibers was found in the median portion of the external layer; these fibers terminated on the capillary loops of the hypophysial portal system. In the caudal division of the median eminence, the CRF-immunoreactive nerve fibers were located in the median to paramedian portions of the external layer. Numerous oxytocin- and vasopressin-immunoreactive nerve fibers were observed evenly distributed throughout the internal layer of the median eminence. In the external layer, a small number of the oxytocin- and vasopressin-containing nerve fibers was found around the capillary loops, particularly in the median to paramedian portions. The distributional patterns of the CRF and the posterior lobe hormones in the hypothalamo-hypophysial system and their functional interrelationship are discussed.

Effect of adrenalectomy and administration of hypertonic saline on the content of aldehyde fuchsin-positive neurosecretory material and posterior lobe hormones in the median eminence and the neural lobe of rats.

The influence of adrenalectomy and administration of hypertonic saline on the amount of vasopressin, oxytocin, and neurophysin contained in the median eminence and the neural lobe of rats was studied by means of the following methods: (i) morphometric and microphotometric analyses of aldehyde fuchsin-stained histological sections of the neurohypophysis; (ii) immunohistochemical demonstration of vasopressin, oxytocin, and neurophysin in the neurohypophysis, and (iii) radioimmunological measurement of vasopressin and oxytocin in extracts of the median eminence and the neural lobe. Adrenalectomy increases the amount of vasopressin and neurophysin in the external layer of the median eminence but does not change the content of oxytocin. It has no influence on the amount of vasopressin, oxytocin, and neurophysin demonstrable in the inner layer of the median eminence and in the neural lobe two weeks after the operation. Hypertonic saline markedly diminishes the vasopressin, oxytocin, and neurophysin content of the inner layer of the median eminence and the neural lobe but reduces only slightly, if at all, the amount of vasopressin and neurophysin in the outer layer of the median eminence. The findings support the concept that osmotic stress reduces only the vasopressin and oxytocin content of the hypothalamus-neural lobe system and has no or only little influence on the vasopressin content of the outer layer of the median eminence.

Immunohistochemical demonstration of the localization of corticotropin releasing factor-containing neurons in the hypothalamus of mammals including primates.

The presence of the CRF-containing neurons in the hypothalamus was investigated in four different species (cats, dogs, pigs, and monkeys) by the peroxidase-antiperoxidase technique using specific antiserum to CRF. In all animals examined, CRF-containing perikarya were found mainly in the paraventricular and supraoptic nuclei, and a small number of the immunoreactive cells were observed in the accessory supraoptic nucleus and the lateral hypothalamic area. The size of the CRF-containing perikarya ranged from 20-35 micron in diameter. These findings suggest that the magnocellular paraventricular and supraoptic nuclei are the center not only of the classical neurosecretory system for the production of the posterior lobe hormones, but also that of the CRF neuronal system.

Effect of water and salt intake on pituitary catecholamines in the rat and domestic pig

The dopamine content of the combined neural and intermediate lobes of the rat pituitary gland was increased when the secretion of posterior lobe hormones was maximally stimulated by a restricted water intake followed by the administration of NaCl in the drinking water (dehydration). This was accompanied by vasodilatation in the posterior lobe and by an increase in the intensity of catecholamine fluorescence in the perivascular nerve fibres. The quantity of noradrenaline in the neural and intermediate lobes, which amounts to about 10% of that of dopamine, was also increased after dehydration. Bilateral removal of the sympathetic superior cervical ganglia did not prevent the rise in pituitary dopamine levels after dehydration but the perivascular catecholamine-containing nerve fibres were no longer detectable. The operation caused a decrease in the noradrenaline content of the neural and intermediate lobes by about 50% in rats on normal water intake and in dehydrated rats. Thus, one half of the noradrenaline present in the neural and intermediate lobes is not contained in vasomotor fibres or other nerve fibres with cell bodies in the superior cervical ganglion. The increase in pituitary dopamine levels after dehydration was also observed in domestic pigs. It is concluded that the increase in the concentration of dopamine in the combined neural and intermediate lobes that follows dehydration and salt-loading does not occur in the perivascular sympathetic nerve fibres and that it may be related to the fall in the pituitary content of oxytocin and vasopressin.

Immunocytochemical localization of the posterior lobe hormones and of their carrier proteins.

Serial sections of vertebrate hypothalami were stained with the immunocytochemical peroxidase-antiperoxidase method. In addition to the single staining method, our double staining method was used, which enabled us to visualize two tissue antigens in single tissue sections. In both staining methods, differentially adsorbed antineurohypophysial hormone sera, anti-somatostatin serum and anti-bovine neurophysin sera were used. The results confirm the one hormone, one neuron hypothesis.

RE-INTRODUCTION AND EVALUATION OF AN ACCURATE, HIGH CAPACITY BIOASSAY FOR MELANOCYTE-STIMULATING HORMONE USING THE SKIN OF ANOLIS CAROLINENSIS IN VITRO

A simple and rapid assay for the quantitative determination of melanocyte-stimulating hormone (MSH) activity, using skin fragments of the lizard Anolis carolinensis in vitro, is described in detail. This assay, in which a quantal response (e.g. induction of a brownish-green colour) can be detected by visual observation, allows determination of MSH activity in up to 50 samples/day by one person, using the skin of one lizard. The mean dose found to induce this colour change was 0-15 ng synthetic alpha-MSH/ml (range 0-02-0-5 ng/ml). The assays shows high accuracy, reproducibility and specificity. Anterior and posterior lobe hormones as well as pituitary catecholamines do not interfere with the determination of pituitary MSH activitymthe method is compared with the assay using hypophysectomized frogs (Rana pipiens) in vivo. Determinations of MSH in pituitary extracts by both methods gave quantitatively similar results when determined with alpha-MSH as the reference substance. However, when beta-seryl MSH was used as a reference, the two assays gave different results for the MSH activity of the pituitary extractsmthis indicates that MSH from the rat pituitary gland has a biological activity similar to that of alpha-MSH rather than to that of beta-seryl MSH.

Neurophysin methylation in extracts of bovine posterior pituitary gland: Hormone binding ability

The highest specific activity of protein carboxymethylase (S-Adenosyl-Lmethionine : protein U-methyltransferase, EC 2.1.1.24) is found in the pituirary gland [ 11. Both lobes of the gland contain the enzyme although the posterior lobe appears to have the greater activity [2]. Recently, it was reported that six of the anterior pituitary hormones were good substrates for pituitary carboxymethylase [ 1 ] . The posterior lobe hormones, oxytocin and vasopressin, were,included in this study but since they lack a free carboxyl group they were not methylated. Together with the high protein carboxymethylase activity, extracts of posterior pituitary glands contain endogenous methyl-acceptor(s) [3]. In the present communication evidence is presented which is consistent with the identification of neurophysin as a major acceptor. The ability of agarose-coupled [Uysinelvasopressin to bind methylated and unmodified protein with similar avidity is discussed.

The relation between the caudo-dorsal region of the preoptic nucleus and the pars nervosa of the pituitary gland in Xenopus lavis tadpoles. An investigation based on hypothalamic lesions.

In order to investigate the relation between the caudo-dorsal region of the preoptic nucleus and the pars nervosa of the pituitary gland in Xenopus laevis tadpoles, hypothalamic lesions were made by means of an electrocoagulation technique. Only lesions in the hypothalamus between optic chiasm and infundibular stem, by which the caudo-dorsal region of the preoptic nucleus was obliterated, resulted in a regression of the pars nervosa. It is concluded that the neurosecretory cells of this caudo-doreal region are responsible for the synthesis of the posterior lobe hormones.

Inhibition of the release of the neurohypophysial hormones of rats by catecholamines, in vitro.

SummarySuperfused horns of uteri removed from rats during artificially induced oestrus were equally sensitive to oxytocin and vasopressin when the superfusion fluid contained MgSO4.H2O, 500 mg/l. This preparation was used to assay the total neurohypophysial hormone released by pairs of posterior lobes of rat pituitary glands in serial 20 minute incubations in vitro. The rate of release of posterior lobe hormone remained constant from the 20th to the 80th minute of incubation in medium containing 500 mg MgSO4.H2O per l. The release rate varied from gland to gland: each pair of glands, therefore, necessarily provided its own control for tests of drug action on release rate. L‐noradrenaline and L‐adrenaline (3 × 10‐6M) inhibited the release of hormone from the neural lobes: the α‐adrenergic blocking agent phentolamine, 5·3 × 10‐6M, may have decreased the resting rate of release of hormone and clearly enhanced the inhibition of release caused by noradrenaline. The β‐blocking agent proprannlol (6·8 × 10‐6M) did not influence the basal rate of hormonal release but potentiated the inhibitory effect of noradrenaline.

The reaction of the preoptic nucleus of Xenopus laevis tadpoles to osmotic stimulation. A fluorescence microscopical investigation.

The development of the preoptic nucleus of Xenopus laevis tadpoles during metamorphosis was studied and the effect of osmotic stimulation on this process investigated. The development of this region was not affected by treatment for one or more days in hypertonic media. It was found that at the end of metamorphosis the neurosecretory cells in the preoptic nucleus are localized in three regions: the rostro-dorsal, the caudo-dorsal and the ventral region. After osmotic stimulation only the neurosecretory cells of the caudo-dorsal region appeared to have reacted, as indicated by their loss of neurosecretory (PIC positive) material. It is concluded that the cells of this region may be involved in the synthesis of the posterior lobe hormones.

The Hypothalamo-Neurohypophysial System and Reproduction

This chapter discusses the hypothalamo-neurohypophysial system (HNS), its afferent pathways, and its role in reproduction. The HNS consists of the magnocellular supraoptic and paraventricular nuclei (SON and PVN), the hypothalamo-neurohypophysial tract (HNT), and the posterior lobe of the pituitary. This system synthesizes, transports, and releases the posterior lobe hormones and their carrier proteins. Many studies on the HNS have concerned the activation of this system by means of osmotic stimuli such as thirsting. In addition, a relationship seems to exist between this osmotically sensitive HNS and reproductive physiology. Although the hypothalamic parvocellular releasing-factor producing system and the magnocellular HNS are anatomically entirely separated, they are functionally strongly related. This relation between the anterior and posterior lobe function could be of importance for the optimal regulation of mechanisms that are necessary for the preservation of the species. The different parameters used in various research disciplines to study hypothalamic synthesis of neurohormones can be compared by their application on the HNS during many physiological stages of hyperactivity. Since hyperactivity can be produced experimentally through neural or hormonal stimuli, this system is an especially suitable model system for research on hypothalamic function.

Quantitative histochemical study on the influence of lactation and changing levels of gonadotropic hormones on rat supraoptic nucleus.

The activity of thiamine diphosphate phosphohydrolase (TPP-ase) was measured by a quantitative histochemical method in a histologically pure supraoptic nucleus (SON) and an adjacent area of the anterior hypothalamus (AH). During lactation, after castration, during early estrus and after LH administration, an increased TPP-ase activity (57-86%) was found in the SON, while no changes were observed in the AH. These results are indicative of an increased synthetic activity in the SON. Consequently, the activity of TPP-ase in the SON can be used as a parameter for posterior lobe hormone production. (Endocrinology 89: 1123, 1971) THE SUPRAOPTIC and paraventricular nuclei (SON and PVN) synthetize the posterior lobe hormones, vasopressin and oxytocin (for a review see ref. 1). In these nuclei the Golgi apparatus responds to osmotic activation by enlargement and changes in organization (24). In line with these morphological findings the spatial distribution of thiamine diphosphate phosphohydrolase (TPP-ase)—the marker enzyme of the Colgi apparatus (5, 6)—increased in the magnocellular nuclei (7). Moreover, an increased TPP-ase distribution was shown during other stimuli for the SON and PVN, i.e., during midpregnancy, parturition, lactation, after gonadectomy, during early estrus and light-induced persistent estrus, and after administration of gonadotropic hormones (8-10). In the present study the quantitative histochemical method of Lowry (11) was applied, since the localizing enzyme histochemical procedure only registers enzyme distribution, which does not implicate changes in enzyme activity. Both procedures have been used during osmotic activation of the SON, and showed the same results (7, 12). To compare both procedures also during other circumstances that activate the neurosecretory nuclei (8-10), the present study deals with the determination of TPP-ase activity during lactation, after castration, during early estrus and after gonadotropic hormone administration. Materials and Methods Wister rats (T.N.O., Zeist, approximately 200 g) were kept in individual cages at 25 C and exposed to 12 hr light daily (from 7 AM to 7 PM). They received tap water and standard chow (Hope Farms) Seven animals were killed at day 10 of lactation together with 7 control animals during metestrus. Using Hypnorm anesthesia (0.1 ml/100 g body wt, im), 7 male rats were castrated and 7 others were sham operated. All animals were killed 2 weeks after operation. Seven female rats were killed during metestrus together with 8 animals in early estrus (characterized by cornified smears together with heavy, distended uteri). Fourteen female rats were ovariectomized, using Hypnorm anesthesia. Starting on the day of operation all animals received 2 jig estradiol benzoate (Dimenformon) daily (0.1 ml, sc) during the entire experimental period. During the last 2 days before sacrifice 7 animals received 150 M-g LH 2 times daily (NIH-LH-S15). The animals were killed 2 hr after the fifth gonadotropic hormone injection. All animals were killed at 10:30 AM. The TPPase activity was determined (see Fig. 1) in dissected pieces of SON (approximately 0.3 M-g) and adjacent anterior hypothalamus (AH, approximately 2\ig), as has been described by Jongkind (12). Enzyme activities are expressed in moles of substrate hydrolyzed/kg dry weight of tissue during 1 hr of incubation at 30 C (MKH units). The results of 3 separate TPP-ase determinations in the SON during the particular experimental condition were combined according to De Jonge (13). The significance of differences between experimental and control groups was calculated using the Student Mest, while these results were distribution free checked by the Wilcoxon test. Received December 30, 1970. 1 LH was kindly provided by the Endocrinology Study Section, NIH.