Plasma 4-pregnene-17α,20α-diol-3-one (17α,20α-dihydroxyprogesterone) and 17α-hydroxyprogesterone in man

1983 ◽  
Vol 102 (2) ◽  
pp. 271-276 ◽  
Author(s):  
Judith A. Whitworth ◽  
Aldona Butkus ◽  
J. P. Coghlan ◽  
D. A. Denton ◽  
Dianne Saines ◽  
...  
Keyword(s):  
Venous Blood ◽  
Plasma Concentrations ◽  
Normal Subjects ◽  
Dietary Sodium ◽  
Lower Amplitude ◽  
Induced Hypertension ◽  
Male Subjects ◽  
Mineralocorticoid Activity

Abstract. Investigation of the mechanisms involved in ACTH induced hypertension in sheep led to delineation of the major role of 4-pregnene-17α,20α-diol-3-one (17α,20α-OHP) in ovine adrenal venous blood. It has been shown in this model of steroid induced hypertension that 17α,20α-OHP is 'hypertensinogenic' i.e. capable of raising blood pressue when infused concurrently with the major mineralocorticoid and glucocorticoid steroid hormones, but in itself it has no significant blood pressure elevating effect and no significant glucocorticoid or mineralocorticoid activity. The present study examines the regulation of 17α,20α-OHP and 17α-hydroxyprogesterone (17-OHP) in man. The plasma concentration of 17α,20α-OHP in normal ambulant subjects (n = 29) bled at 08.00 to 10.00 h was 14.5 ± 0.8 nmol/l compared with 17-OHP 7.8 ± 0.6 nmol/l. Administration of ACTH (20 μg/kg/day) to normotensive male subjects (n = 6) produced after 5 days of rise in 17α,20α-OHP from 16.6 ± 2.2 to 48.9 ± 7.9 nmol/l and in 17-OHP from 10.9 ± 1.12 to 29.3 ± 4.2 nmol/l. In normal subjects, 17α,20α-OHP had a diurnal rhythm similar to that of cortisol but of lower amplitude. Plasma concentrations of both steroids rose with stepped 30 min ACTH infusions and were suppressed by dexamethasone administration. Angiotensin II infusion, dietary sodium restriction and 9α-fluorocortisol administration had no effect on plasma 17α,20α-OHP. There was no change in 17α,20α-OHP throughout the menstrual cycle but 17-OHP increased during the luteal phase of the cycle. 17-OHP was lower in women on oral contraceptives than in control women, but values for 17α,20α-OHP were unchanged. The mean plasma clearance rate for 17α,20α-OHP in 3 normal subjects was 30.2 l/day/kg, similar to that for aldosterone (31.2 l/day/kg). Unlike the sheep there was no in vitro conversion of 17-OHP to 17α,20α-OHP in human blood. These studies show that 17α,20α-OHP is present in human plasma in higher concentration than 17-OHP. The secretion of 17α,20α-OHP appears to be primarily under the control of ACTH.

Effect of [Asu,]eel calcitonin on prolactin release in normal subjects and patients with prolactinoma

1985 ◽  
Vol 108 (3) ◽  
pp. 297-304 ◽  
Author(s):  
Hidesuke Kaji ◽  
Kazuo Chihara ◽  
Naoto Minamitani ◽  
Hitoshi Kodama ◽  
Tetsuya Kita ◽  
...  
Keyword(s):  
Body Weight ◽  
Bolus Injection ◽  
Normal Subjects ◽  
Regular Insulin ◽  
Prolactin Release ◽  
Saline Administration ◽  
The Central Nervous System ◽  
Plasma Prl ◽  
Male Subjects

Abstract. The effect of [Asu]eel calcitonin (ECT), an equipotent analogue of eel CT, on prolactin (Prl) secretion was examined in 12 healthy male subjects and in 6 patients with prolactinoma. In healthy subjects, ECT (0.5 μg/kg body weight · h) or saline was infused for 2 h and TRH was injected iv as a bolus of 500 μg at 1 h of ECT or saline administration. ECT did not affect basal Prl levels during 1 h of infusion. TRH caused a significant increase of plasma Prl with peak values of 75.2 ± 11.6 ng/ml in ECT-infused subjects, which did not differ from those infused with saline (68.5 ± 8.3 ng/ml). Next, an iv bolus injection of regular insulin (0.1 U/kg body weight) was followed by an infusion of ECT or saline alone. Plasma Prl peaks after hypoglycaemic stress were significantly lower in ECT-infused subjects than those in saline-injected controls (ECT, 16.5 ± 3.1 vs 33.5 ± 9.6 ng/ml, P < 0.05). In patients with prolactinoma, basal levels of plasma Prl ranging from 42.0–4130 ng/ml failed to change during iv infusion of ECT. Moreover, ECT (10−9–10−6m) did not affect Prl release from prolactinoma tissues perifused in vitro. These findings suggest that ECT may not act directly on the pituitary to modify Prl release. Rather, peripherally administered ECT appears to suppress Prl release via the central nervous system.

Oestrogens in breast tumours and fat

1989 ◽  
Vol 95 ◽  
pp. 161-168
Author(s):  
J. H. H. Thijssen ◽  
M. A. Blankenstein
Keyword(s):  
Biological Effects ◽  
Plasma Concentrations ◽  
Normal Breast ◽  
Malignant Tumours ◽  
Breast Tumours ◽  
Two Parameters ◽  
Breast Tissues

SynopsisThe levels of endogenous steroids in the target tissues are thought to be more closely related to the biological effects than their concentrations in plasma. Therefore studies on oestrogen levels in malignant and non-malignant breast tissues (expressed per g wet weight) were conducted and the following conclusions were drawn:(1) malignant tumours contained higher oestradiol levels than normal or benign breast tissues, whereas oestrone levels were more comparable;(2) in contrast to the large decrease in plasma concentrations after menopause, the levels of oestradiol in tumours and in normal breast tissue did not change with advancing age;(3) the oestradiol levels in breast tissues were lower than in uterine tissues, particularly in women before menopause; oestrone levels were very similar in all tissues studied;(4) the mean oestradiol level was higher in oestrogen-receptor-positive tumours, but no correlation between the two parameters was found;(5) preliminary results indicated lower oestradiol levels in tumours obtained from countries with a lower incidence of breast cancer;(6) as far as available, oestrone levels were comparable and those of oestradiol were lower in fat tissues than in breast tumours;(7) neither in vitro studies with breast tumours, nor in vivo results using myometrial tissues support a prominent role of the metabolism of oestrogens at the 16α-position in the development of tumours;(8) the role of local factors in the production, retention and metabolism of oestradiol in the breast remains to be elucidated.

The Role of β2-Glycoprotein I in the Clearance of Platelet Microvesicles.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 145-145
Author(s):  
Hanan Abdel-Monem ◽  
Swapan Kumar Dasgupta ◽  
Anhquyen Le ◽  
Anthony Prakasam ◽  
Perumal Thiagarajan
Keyword(s):  
Plasma Proteins ◽  
Plasma Concentrations ◽  
Major Protein ◽  
Maximal Effect ◽  
Dependent Manner ◽  
Anionic Phospholipid ◽  
Concentration Dependent Manner ◽  
Glycoprotein I

Abstract Abstract 145 The physiological function of β2-glycoprotein I is unclear and several studies suggest a role in the clearance of anionic phospholipid containing membranes. Anionic phospholipid containing liposomes are cleared rapidly from the circulation by the reticuloendothelial cells. In rats, uptake of liposomes by Kupffer cells requires that the liposomes bind to plasma proteins. In mice, the clearance of liposomes from the circulation is related to their ability to interact with plasma proteins. β2-glycoprotein I was identified as a major protein associated with rapid clearance of liposomes and pretreating the mice with antiβ2- glycoprotein I antibodies was found to significantly increase the half-life of the liposome. In vitro, β2-glycoprotein I was also shown to promote the phagocytosis of phosphatidylserine containing liposomes and apoptotic tumor cells. In conditions associated with increased microvesicles generation such as disseminated intravascular coagulation, plasma levels of β;2-glycoprotein I was reduced presumably due to its consumption. Antibodies to β2 glycoprotein I are frequently seen in patients with systemic lupus erythematosus and at times, in otherwise normal individuals. A subset of these antibodies prevents the assembly of the prothrombinase and the tenase complexes on phospholipid membrane, leading to the lupus anticoagulant effect. The presence of these antibodies is clinically very significant, as individuals harboring these antibodies are at risk for thromboembolic manifestations. We studied the role of β-glycoprotein I in the clearance of procoagulant platelet microvesicles and the effect of the auto antibodies in the phagocytosis of platelet microvesicles. We labeled β2-glycoprotein I with BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene)-hydrazide and β2-glycoprotein I incorporated 1.8 mole of BODIPY /mole. Labeling of β2-glycoprotein I with BODIPY did not change the binding efficacy of β2-glycoprotein I to cardiolipin as determined by Elisa assay. Binding of BODIPY-β2-glycoprotein I to platelet microvesicles was analyzed by flow cytometry. BODIPY- β2-glycoprotein I bound to phosphatidylserine-expressing platelet microvesicles in a concentration-dependent manner. Binding was inhibited by 50 fold molar excess of unlabeled β2-glycoprotein I, annexin A5 and the phosphatidylserine-binding C1C2 fragment of lactadherin. β2-glycoprotein I also promoted the phagocytosis of platelet microvesicles by THP-1 derived macrophages in vitro at physiological plasma concentrations with a half maximal effect at ∼10 ug/ml. β2-glycoprotein I-mediated phagocytosis was inhibited by annexin V and the C1C2 fragment of lactadherin. Furthermore, immunoaffinity purified β2-glycoprotein I-dependent antiphospholipid antibodies from 5 patients inhibited the phagocytosis in a concentration dependent manner. These studies suggest β2-glycoprotein I binding to phosphatidylserine-expressing procoagulant platelet microvesicles promotes their clearance by macrophages and autoantibodies to β2-glycoprotein I inhibit the process. The predictive value of antiβ-2 glycoprotein I for thrombosis is highly variable but the correlation is stronger in patients with lupus. In lupus, there is impaired clearance of procoagulant apoptotic cells. β2-glycoprotein I may have a significant role in their clearance and antibodies to β2-glycoprotein I may causally related to the thrombosis in these patients by inhibiting the clearance. Disclosures: No relevant conflicts of interest to declare.

In vitro synthesis of antibodies to acetylcholine receptor by peripheral blood cells: Role of suppressor T cells in normal subjects

Neurology ◽  
1984 ◽  
Vol 34 (6) ◽  
pp. 802-802 ◽  
Author(s):  
R. P. Lisak ◽  
C. Laramore ◽  
A. I. Levinson ◽  
B. Zweiman ◽  
A. R. Moskovitz ◽  
...  
Keyword(s):  
T Cells ◽  
Acetylcholine Receptor ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Normal Subjects ◽  
Peripheral Blood Cells ◽  
Suppressor T Cells ◽  
In Vitro Synthesis

Effect of Single and Combined Infusions of Angiotensin II and Aldosterone on Colonic Potential Difference, Blood Pressure and Renal Function, in Patients with Adrenal Deficiency

1975 ◽  
Vol 48 (3) ◽  
pp. 219-226
Author(s):  
A. D. Efstratopoulos ◽  
W. S. Peart
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Plasma Concentrations ◽  
Young Male ◽  
Normal Subjects ◽  
Potential Difference ◽  
Normal Male ◽  
Adrenal Deficiency ◽  
Increased Sensitivity ◽  
Male Subjects

1. The effect of single and combined infusions of angiotensin and aldosterone on colonic potential difference, blood pressure and renal function was studied in two normal male subjects and four female patients with adrenal deficiency maintained only on cortisone. 2. Aldosterone had its usual effect on colonic potential difference and it was possible to show that angiotensin had a small but definite effect of its own in the absence of aldosterone. The two hormones produced a summation response when given together. 3. The effects on renal function in two normal young male subjects were similar to those known previously. The response of the patients was different and probably reflected a number of factors, such as age, sex and long-standing adrenal deficiency. 4. Although the numbers were small, both normal subjects and patients showed a significantly greater rise of blood pressure with combined infusions of angiotensin and aldosterone than with angiotensin alone. The plasma concentrations of angiotensin were similar with both types of infusion, and so increased sensitivity to angiotensin in the presence of aldosterone is postulated.

THE ROLE OF A FEEDBACK MECHANISM IN THE REGULATION OF ALDOSTERONE SECRETION IN THE RAT

1973 ◽  
Vol 73 (2) ◽  
pp. 282-288
Author(s):  
L. Debreceni ◽  
B. Csete
Keyword(s):  
Marked Decrease ◽  
Feedback Regulation ◽  
Feedback Mechanism ◽  
The Other ◽  
Dietary Sodium ◽  
Sodium Restriction ◽  
Aldosterone Secretion ◽  
Aldosterone Production

ABSTRACT The effect of prolonged aldosterone and DOC treatment in the in vitro aldosterone production was studied in the rat. When the animals were supplied with food containing 16.5 mEq./100 g of sodium, both aldosterone and DOC treatment led to a marked decrease in aldosterone production. On the other hand, under dietary sodium restriction both aldosterone and DOC treatment failed to induce a suppression of the elevated aldosterone production. On the basis of these findings, it seems that a sufficient sodium supply of the organism is necessary for the control of aldosterone secretion either by an increase of aldosterone production or DOC treatment if any feedback regulation is involved in the mechanism controlling aldosterone secretion.

scholarly journals Do patients with thromboembolic disease have circulating platelet aggregates?

Blood ◽  
1984 ◽  
Vol 64 (1) ◽  
pp. 205-209 ◽  
Author(s):  
FH Kohanna ◽  
MH Smith ◽  
EW Salzman
Keyword(s):  
Platelet Rich Plasma ◽  
Venous Blood ◽  
Adenosine Diphosphate ◽  
Normal Subjects ◽  
Thromboembolic Disease ◽  
Circulating Platelet Aggregates ◽  
Platelet Aggregates ◽  
Lower Ratio

Reports of circulating platelet aggregates (ie, microemboli) in thromboembolism and other vascular disorders are based on a method (Wu and Hoak , 1974) in which venous blood is collected via scalp vein needle and tubing into either formaldehyde, which fixes aggregates, or EDTA, which disperses them. The ratio of platelet counts in platelet- rich plasma (PRP) from the two blood samples after centrifugation is interpreted as a measure of platelet aggregates in the circulation in vivo. We compared this standard Wu and Hoak technique with a modified one, in which blood was drawn directly into a syringe, and with a third method that avoided centrifugation by counting single platelets in whole blood. Both modified techniques could detect aggregates generated in vitro with adenosine diphosphate (ADP). In 12 normal subjects, the three methods were equivalent, but in 37 patients with thromboembolic disorders, the standard Wu and Hoak method gave a lower ratio than the other methods. Similar results were found in a subset of eight patients with myocardial infarction. Heparin treatment of patients did not influence the results. The data suggest that formation of platelet aggregates occurred during venipuncture. Platelets may be hyperactive in patients with thromboembolic disease and may form aggregates in vitro during collection, but the concept of chronic microembolism in such patients should be reassessed.

scholarly journals Bone Marrow Response to Erythropoietin in Polycythemia Vera and Chronic Granulocytic Leukemia

Blood ◽  
1972 ◽  
Vol 39 (3) ◽  
pp. 341-346 ◽  
Author(s):  
Stanley Zucker ◽  
Diane M. Howe ◽  
Lewis R. Weintraub
Keyword(s):  
Bone Marrow ◽  
Polycythemia Vera ◽  
Bone Marrow Cells ◽  
Normal Subjects ◽  
Normal Range ◽  
Chronic Granulocytic Leukemia ◽  
Iron Incorporation ◽  
Granulocytic Leukemia

Abstract The regulation of erythropoiesis was studied in patients with polycythemia vera and chronic granulocytic leukemia (CGL). An in vitro culture system was employed to determine the response of bone marrow cells to erythropoietin. In normal subjects, iron incorporation into heme (during the 18th to 22nd hr of culture) was increased by 35% (mean) in erythropoietin-treated cultures as compared to control cultures. Erythropoietin was ineffective in stimulating iron incorporation into heme in five patients with polycythemia vera. The marrow response to erythropoietin in vitro was within the normal range in three patients with CGL (37% stimulation). Thus, the role of erythropoietin in the control of erythropoiesis in myeloproliferative syndromes appears variable.

Measurement of lactate formation from glucose using [6-3H]- and [6-14C]glucose in humans.

1990 ◽  
Vol 259 (3) ◽  
pp. E397 ◽  
Author(s):  
A Virkamäki ◽  
I Puhakainen ◽  
N Nurjhan ◽  
J E Gerich ◽  
H Yki-Järvinen
Keyword(s):  
Lactate Dehydrogenase ◽  
Plasma Glucose ◽  
Venous Blood ◽  
Normal Subjects ◽  
Glutamic Pyruvic Transaminase ◽  
Plasma Lactate ◽  
Lactate Formation ◽  
Extrahepatic Tissues ◽  
Specific Activities

To assess the validity of determining the origin of plasma lactate from the ratio of lactate and glucose specific activities (SA) during infusion of labeled glucose, normal subjects received infusions of [6-3H]- and [6-14C]glucose for 4 h after a 12 h fast, and, on another day, cold glucose labeled with both tracers during 4-6 h of hyperinsulinemia (approximately 650 microU/ml). Basally, less lactate was derived from plasma glucose when measured with [6-3H]glucose (27 +/- 2%) than with [6-14C]glucose (40 +/- 2%, P less than 0.001). Insulin did not increase the percent of lactate derived from plasma glucose when measured with [6-3H]glucose (29 +/- 2%) but did increase when measured with [6-14C]glucose (60 +/- 4%). The arterialized blood (A) [3H]lactate SA was 30-40% higher (P less than 0.01) than deep venous blood (V) [3H]lactate SA, whereas A and V [14C]lactate SA were similar. During conversion of alanine to lactate with glutamic-pyruvic transaminase (GPT) and lactate dehydrogenase (LDH) in vitro, 32 +/- 2% of 3H in [3-3H]alanine was found in water and 68 +/- 2% in lactate. During infusion of [6-3H]- and [6-14C]glucose, the ratio of [14C]alanine to lactate SA (0.88 +/- 0.05) was less than the ratio of [3H]alanine to lactate SA (0.31 +/- 0.03, P less than 0.001). In conclusion 1) loss of 3H relative to 14C from position 6 in glucose occurs during lactate formation in extrahepatic tissues possibly due to the GPT reaction (alanine conversion to pyruvate), and 2) even under supraphysiologic hyperinsulinemic conditions not all of plasma lactate originates from plasma glucose.

scholarly journals Zinc deficiency induces hypertension by promoting renal Na+ reabsorption

2019 ◽  
Vol 316 (4) ◽  
pp. F646-F653 ◽  
Author(s):  
Clintoria R. Williams ◽  
Monisha Mistry ◽  
Aswathy M. Cheriyan ◽  
Jasmine M. Williams ◽  
Meagan K. Naraine ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Diseases ◽  
Adult Mice ◽  
Induced Hypertension ◽  
Surface Localization ◽  
Uptake Activity ◽  
Tubule Cells ◽  
Role Of Zn

Zn2+ deficiency (ZnD) is a common comorbidity of many chronic diseases. In these settings, ZnD exacerbates hypertension. Whether ZnD alone is sufficient to alter blood pressure (BP) is unknown. To explore the role of Zn2+ in BP regulation, adult mice were fed a Zn2+-adequate (ZnA) or a Zn2+-deficient (ZnD) diet. A subset of ZnD mice were either returned to the ZnA diet or treated with hydrochlorothiazide (HCTZ), a Na+-Cl− cotransporter (NCC) inhibitor. To reduce intracellular Zn2+ in vitro, mouse distal convoluted tubule cells were cultured in N,N,N′,N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN, a Zn2+ chelator)- or vehicle (DMSO)-containing medium. To replete intracellular Zn2+, TPEN-exposed cells were then cultured in Zn2+-supplemented medium. ZnD promoted a biphasic BP response, characterized by episodes of high BP. BP increases were accompanied by reduced renal Na+ excretion and NCC upregulation. These effects were reversed in Zn2+-replete mice. Likewise, HCTZ stimulated natriuresis and reversed BP increases. In vitro, Zn2+ depletion increased NCC expression. Furthermore, TPEN promoted NCC surface localization and Na+ uptake activity. Zn2+ repletion reversed TPEN effects on NCC. These data indicate that 1) Zn2+ contributes to BP regulation via modulation of renal Na+ transport, 2) renal NCC mediates ZnD-induced hypertension, and 3) NCC is a Zn2+-regulated transporter that is upregulated with ZnD. This study links dysregulated renal Na+ handling to ZnD-induced hypertension. Furthermore, NCC is identified as a novel mechanism by which Zn2+ regulates BP. Understanding the mechanisms of ZnD-induced BP dysregulation may have an important therapeutic impact on hypertension.

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