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Biomedical subjects

B Koch

Publications and source records attributed to B Koch.

At least 199 records · Page 11Linked to original sources

Modulation by transcortin-like binding sites of uptake and distribution of glucocorticoids by dispersed pituitary cells.

The influence of transcortin-like (TL) binding sites on uptake and distribution of glucocorticoids by dispersed pituitary cells was investigated. TL material, which combines corticosterone (CORT), but not dexamethasone (DEX), was previously found to be present on cell membranes and in cytosol of hypophysis. Exposure of cells at 0 degrees brought about striking differences in steroid binding, as labeled CORT was taken up more rapidly and to a significantly greater extent than DEX. This resulted from a higher concentration of binding sites and not from a difference in binding affinity. At 25 and 37 degrees, while the same relationship was apparent during the early events of steroid interaction with the cell, binding of DEX increased gradually with incubation time and finally exceeded that of the natural steroid. Also, time-course studies on nuclear translocation showed a biphasic pattern, which closely paralleled that of whole-cell binding. Interestingly, treatment of rats with transcortin antiserum caused a decrement of pituitary TL sites, as well as of CORT translocation. We conclude that the TL binder, which is probably of plasma origin, may be actively involved in the process of uptake and cellular distribution of corticosteroids in the pituitary gland.

Animals↗

Evidence for a possible dopaminergic control of pituitary alpha-MSH during ontogenesis in mice.

This study was aimed at determining the alpha-MSH and ACTH contents of the neurointermediate lobe (NIL) of the mouse hypophysis during ontogenesis, as well as the ability of the gland, incubated in a perfusion system, to respond to dopamine (DA) and high potassium (K+). We showed that: (1) the NIL content of alpha-MSH exhibited a biphasic pattern of evolution, characterized by a dramatic increase appearing between postnatal days 3 and 5. By contrast, NIL ACTH content followed a completely different pattern of evolution; (2) both DA and high K+ reversibly inhibited MSH release from superfused NIL, the latter effect being more pronounced with the use of pituitaries from 7-day-old than from 1-day-old mice; (3) the inhibitory influence of high K+ was impaired by haloperidol pretreatment. From these data, as well as from morphological observations, it appears that functional DA receptors seem to be present on melanotrophs of the developing hypophysis in mice and that the increase in alpha-MSH in IL cells observed shortly after birth may result from the onset of inhibitory influence exerted by dopaminergic innervation on hormonal secretion. This view, however, does not preclude possible effects of other hypothalamic releasing and/or inhibiting factors.

Adrenocorticotropic Hormone↗

Ontogenesis of glucocorticoid receptors in anterior pituitary gland: transient dissociation among cytroplasmic receptor density, nuclear uptake, and regulation of corticotropic activity.

The present investigation was undertaken to define the developmental pattern of glucocorticoid binding to the anterior pituitary gland and ascertain whether that binding correlated to modulation of corticotropin-releasing factor-induced release of ACTH. Scatchard analysis of data revealed the presence in cytosol (besides classical receptor sites interacting with both [3H]dexamethasone and [3H]corticosterone) of a transcortin-like component binding only the natural steroid. Whereas the number of sites of the former binder was not significantly altered during maturation and remained close to the adult value (276 +/- 12 fmol/mg protein), that of the latter declined dramatically after birth and rose again after postnatal day 10. The apparent Kd, however, remained unchanged. Transfer of te [3H]dexamethasone-receptor complex to nuclei of pituitary cells from neonates 2-6 days of age was found to be 20% that of adults despite the presence of comparable concentrations of receptor sites. Mixing experiments carried out with cytosol and nuclear fractions from different origins pointed to the cytoplasmic compartment as being implicated in this discrepancy. It was not until after postnatal day 10 that nuclear transfer reached mature levels. Although the extent of nuclear uptake and the magnitude of inhibition of ACTH secretion, as judged by means of a perifusion system, correlated well in hypophyses from 10- to 30-day-old neonates and adults, steroid binding and induction of biological response at earlier time points were less closely related. The results indicate the existence during development of a transient dissociation between cytosol and nuclear binding of corticosteroids by the anterior pituitary as well as between the latter process and blockade of ACTH release. These data are discussed in connection with the postnatal period nonresponse to stress. (Endocrinology 108: 591, 1981)

Adrenocorticotropic Hormone↗

[Vasopressin and "CRF" in the regulation of ACTH secretion by the anterior and intermediate lobes of the pituitary gland (author's transl)].

The aim of this review was to summarize the present state of knowledge concerning the mode of action of vasopressin (VP) and the putative corticotropin releasing factor (CRF) on ACTH secretion from the anterior and intermediate lobes of the pituitary gland. In vitro data show that although both CRF and VP enhanced release of anterior pituitary ACTH, the pattern of hormonal release, based on kinetical and dose-dependent studies, appeared to be different. Also, the effect of VP most probably was mediated by specific putative receptor sites. In contrast, VP was found not to alter ACTH secretion from the intermediate lobe; that secretion seems to be regulated by CRF-like material and neurotransmitters. The importance of VP as a corticotropin agent is discussed.

Adrenocorticotropic Hormone↗

Thermosensitivity of the membrane potential of normal and simian virus 40-transformed hamster lymphocytes.

The effects of temperature in the fever range (37-42 degrees) on the membrane potentials of normal and simian virus 40-transformed hamster lymphocytes were analyzed. The transmembrane distributions of radiolabeled triphenylmethylphosphonium and thiocyanate were measured, and they provide upper and lower limits for the normal cell membrane potential at 37 degrees of -48 +/- 6 (S.D.) and -31 +/- 5 mV and for the tumor cells, -36 +/- 4 and -19 +/- 2 mV. The mitochondrial contribution to the triphenylmethylphosphonium-measured membrane potential, 5 to 10 mV for both splenocytes and simian virus 40-transformed lymphocytes, was estimated by utilizing antimycin A and carbonylcyanide-m-chlorophenylhydrazone to inhibit generation of a mitochondrial membrane potential. Incubation for 1 to 2 hr at 38-42 degrees resulted in a 6- to 15-mV depolarization of normal cells and a 2- to 6-mV hyperpolarization of tumor cells. Both depolarization and hyperpolarization were fully reversible by subsequent incubation at 37 degrees and insensitive to antimycin A and carbonyl-cyanide-m-chlorophenylhydrazone. The membrane potential of normal splenocytes when measured with triphenylmethylphosphonium at 37 degrees was depolarized by 35% with 1 mM ouabain and thermally induced depolarization was blocked. The membrane potential of tumor cells at 37 degrees was insensitive to ouabain; however, the hyperpolarization at 40 degrees was inhibited. The membrane potential of normal lymphocytes stimulated with phytohemagglutinin was depolarized relative to that of nonstimulated control cells and assumed the thermal response characteristics of tumor cells.

Animals↗

Glucocorticoid binding and control ACTH secretion.

This report attempts to summarize the present state of knowledge concerning interaction of glucocorticoids with brain and pituitary receptors, in relation to induction of specific biological effects. It examines the properties of the receptors, emphasizing the fact that transcortin-like binding molecules are present on the cell membrane in the pituitary gland. Also, it considers the functional aspects of the mechanism of action of steroids, including control, occupancy and heterogeneity of binding sites, as well as correlation with regulation of ACTH release.

Adrenocorticotropic Hormone↗

Evidence for a direct inhibitory effect of morphine on the secretion of posterior pituitary hormones.

The effect of morphine and naloxone on vasopressin and oxytocin release from incubated neurointermediate lobe and pars nervosa of rat pituitaries were investigated. It was shown that morphine and endorphins blocked hormonal output and that this inhibitory action was reversed by naloxone. It is concluded that opiates exert a direct inhibitory influence on vasopressin and oxytocin secretions from the neurohypophysis.

Adrenocorticotropic Hormone↗

Computerized tomography in cerebral-palsied children.

Of a total of 160 patients with cerebral palsy, 80 were studied by computerized tomography. In the congenital group, abnormal studies were found in two of the 12 patients with diplegia, 16 of 18 with hemiplegia, 14 of the 18 with quadriplegia and five of the seven with atonic diplegia. 18 of 21 patients with acquired disease had abnormal CT scans. Computerized tomography is a useful tool for demonstrating the anatomical lesion responsible for cerebral-palsied patients' clinical findings. It is also useful in making a prognosis of functional outcome, and in defining lesions which are correctable by neurosurgery.

Adolescent↗

Involvement of vasopressin in corticotropin-releasing effect of hypothalamic median eminence extract.

Incubation of anterior pituitary (AP) fragments of rats was used to determine the specific role played by vasopressin (VP) in the overall effect of crude hypothalamic median eminence (HME) extract on ACTH release. Using the property of an AVP antiserum (AS) to completely abolish the CRF-like effect of hypothalamic VP without apparently affecting the effect of CRF, we show that under specific incubation conditions, the effect of the two secretagogues are additive at the pituitary level. ACTH secretion of pituitaries was enhanced when incubation was carried out in the presence of VP together with a maximum effective dose of VP-free HME extract (from Brattleboro rats). These observations favor the hypothesis that VP and CRF have different receptor sites in the anterior pituitary.

Adrenocorticotropic Hormone↗

In vitro regulation of ACTH release from neurointermediate lobe of rat hypophysis. III. Effect of potassium (K+), calcium (Ca++) and dibutyryl cyclic 3',5'-adenosine monophosphate (dbc-AMP).

Alterations in the ionic composition of the medium and different secretagogues have been used in order to study the mechanism of release of ACTH from superfused neurointermediate lobes (NIL) of rat hypophysis. We showed that: (a) a tenfold increase of K+ in the medium caused a reversible and repeatable stimulation of the ACTH release; (b) removal of Ca++ reversibly abolished the stimulating effect of high K+; (c) removal of Ca++ had no effect on the stimulating effect of a hypothalamic extract (HE); (d) in the latter case, a reversible significant weakening was obtained by the addition of EDTA in the Ca++-free medium; (e) dbc-AMP caused a reversible and repeatable stimulation of the ACTH release; (f) comparable results were obtained for anterior lobes (AL) superfused in the same conditions. From these data we can conclude that Ca++ is necessary for the stimulation of the hormonal release and that factors such as K+ or dbc-AMP can mimic the in vitro stimulating effect of a HE. Similarities, which appear in this study, between the modulation of the ACTH release from NIL and AL, led us to support the idea that, in vivo, a release of ACTH from the NIL, may occur in physiological conditions.

Adrenocorticotropic Hormone↗

[Specificity of the effect of vasopressin at the anterior pituitary level (author's transl)].

The present investigation was conducted in order to get more insight into the mechanism of action of vasopressin (VP) on ACTH secretion and characterize VP interaction with putative receptor sites at the level of the anterior pituitary gland. The experimental procedure consisted of increasing ACTH release from incubated pituitary fragments as induced by VP in the presence or absence of oxytocin (OT) and various releasing factors. Our results show that, whereas OT was able to depress VP-induced release of ACTH (Fig. 2), TRF (Fig. 3), LH-RH (Fig. 4) and crude "CRF" extract (Fig. 1) it did not exhibit any significant inhibitory effect. This provides indirect evidence for the presence of specific pituitary sites for VP and related peptides such as OT. The latter, however, was devoided of corticotrophic releasing properties.

Adrenocorticotropic Hormone↗

[Goitres with "cold" nodules in an endemic goitre area (author's transl)].

Of 339 goitres with "cold" nodules 17.7% were histologically malignant. Related to all cold nodules which were examined, this suggest a "true" malignancy rate of nodules of about 0.4%. The risk of malignancy is highest in patients over 60 years of age. The malignancy rate was high, at 23%, in cold nodules of recurrent goitres. Fine-needle aspiration biopsy pre-operatively will correctly diagnose over 90% of malignant nodules.

Age Factors↗