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Biomedical subjects

J W Funder

Publications and source records attributed to J W Funder.

At least 289 records · Page 16Linked to original sources
PubMed1981

Frequency of 1,25-dihydroxyvitamin D3 receptor in human breast cancer.

Receptors for 1,25-dihydroxyvitamin D3 have been shown to exist in cultured breast cancer cells and in primary breast cancers. It is reported here that 1,25-dihydroxyvitamin D3 receptor (1,25-DR) was present in 80% of 54 unselected breast cancers. The concentration of 1,25-DR in the 43 receptor-positive tumors was 1.9 +/- 0.4 fmol/mg protein (S.E.). There was no correlation between 1,25-DR presence or concentration and the age of the patient or the concentration of estrogen, progesterone, androgen, or glucocorticoid receptors. 1,25-DR was also found in two of three renal cortical carcinomas but only in three of 14 gastrointestinal tract carcinomas. The relatively low concentration of 1,25-DR in these breast cancers, compared with that found in cultured breast cancer cells, is partially explained by incomplete "exchange" with occupied receptors. Since the serum vitamin D-binding protein is not precipitated from serum itself or from tissue homogenates using the polyethylene glycol method, artifactual 1,25-DR levels due to the inevitable contamination of tissue specimens with this protein can be excluded. These findings indicate that 1,25-DR is not a nonspecific marker of cancer. The high frequency of 1,25-DR in the breast cancers may be related to the calcium-transporting ability of breast cancer cells which allows them to grow as osteolytic metastases.

Adult↗
PubMed1980

19-nor analogs of adrenal steroids: mineralocorticoid and glucocorticoid receptor activity.

The effect of absence of the C-19 methyl group from five adrenal steroids has been studied in terms of their affinity for mineralocorticoid (MR) and glucocorticoid receptors (GR). In MR assays, 19-nordeoxycorticosterone and 19-norprogesterone showed 3-fold higher affinity for MR than did their respective parent steroids; 19-norcortisol had 1.5 times the affinity of cortisol for MR. In contrast, corticosterone and 19-nororticosterone showed equal affinity, and 19-noraldosterone showed less than 1% the MR activity of aldosterone. In GR assays, the absence of the C-19 methyl group from progesterone increased GR affinity 3-fold and deoxycorticosterone affinity 1.5-fold. In contrast, the other 19-nor steroids showed decreased affinity vis à vis their parent compounds (19-norcorticosterone, 30%; 19-norcortisol, 10%; 19-noraldosterone, < 1%). These findings suggest that while the 19-nor analogs of 11-deoxy steroids are consistently more active than their parent steroid, the 19-nor 11-oxygenated adrenal steroids show no predictable pattern of binding for MR or GR.

Aldosterone↗
PubMed1980

Intimal lesions in rat caudal artery. Ablation, replacement, and receptor studies on the protective effects of estrogen.

The incidence of spontaneous lesions of the intima in the rat caudal artery is significantly higher in male than in female Wistar rats at 12 weeks of age. After gonadectomy at 5 weeks, lesions in both sexes at 12 weeks reach a level intermediate between those seen in age-matched intact males and females. After gonadectomy at 5 weeks, lesions in both male and female rats are unaffected by testosterone administration but are reduced to below female control levels by diethylstilbestrol. In contrast, diethylstilbestrol administration does not significantly reudce lesion incidence in intact male rats. Binding studies provided no evidence of estrogen-binding sites in cytosol from caudal arteries, but heart and kidney cytosols from both male and female rats contain a single class of high affinity (10(-10)M) binding sites with specificity characteristic of estrogen receptors. Longitudinal studies (4-11 weeks of age) provided no evidence for a change in receptor profile as a factor contributing to the increased lesion incidence in mature male rats.

Animals↗
PubMed1979

Hormone receptors.

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Adenylyl Cyclases↗
PubMed1979

Decreased cardiac beta-adrenergic receptors in deoxycorticosterone-salt and renal hypertensive rats.

The development of experimental deoxycorticosterone-salt (DOCA-salt) and renal artery clip hypertension in rats is associated with alterations in the sensitivity of the myocardium to adrenergic stimulation. We studied beta-adrenergic receptors and isoproterenol-stimulated adenylate cyclase in myocardial membranes from hypertensive rats to determine whether this altered sensitivity is associated with any change in beta-adrenergic receptors. The specific binding of the beta-adrenergic antagonist, 125I-iodohydroxybenzylpindolol, was used to measure numbers and affinities of receptors in myocardial membrane preparations. Cardiac membranes from both DOCA-salt and renal hypertensive rats showed significantly fewer beta-receptors than did membranes from control, normotensive rats. Receptor affinity remained unchanged. This decrease was from 110 +/- 19 to 49 +/- 5 fmol/mg protein for DOCA-salt hypertension and from 110 +/- 18 to 75 +/- 16 fmol/mg protein for renal artery clip hypertension. Isoproterenol-stimulated adenylate cyclase activity also was lower in membranes from hypertensive rats, whereas basal and fluoride-stimulated activities were unchanged.

4-Nitrophenylphosphatase↗
PubMed1979

The mineralocorticoid antagonist activity of an 11 beta,18-oxidopregnane.

Removal of the 18-hydroxy group of the hemiacetal form of aldosterone transforms its activity from that of pure agonist to predominant antagonist. The 18-deoxy derivative possesses one third of the binding affinity of aldosterone for the cytoplasmic mineralocorticoid receptor of rat kidney and exhibits an approximate 2:1 antagonist to agonist ratio in both toad bladder and adrenalectomized rat bioassay systems. The promising properties of the 11 beta,18-oxidopregnane tested included very low androgen receptor affinity and approximately equal effectiveness in vitro and in vivo in displacing aldosterone from mineralocorticoid-binding sites in the rat.

Aldosterone↗
PubMed1979

Cimetidine, a histamine H2 receptor antagonist, occupies androgen receptors.

The histamine H2 receptor antagonist cimetidine is in increasing usage in the medical management of peptic ulcer. In clinical trials, its most frequent side effect is gynecomastia. Such estrogenic/antiandrogenic manifestations are well known side effects of treatment with digitoxin or spirolactones. Both of these drugs share a common skeleton with the steroid hormones and have been shown to occupy estrogen and/or androgen receptors. Cimetidine has no measurable affinity for rat uterine estradiol receptors, but competes for tritiated dihydrotestosterone-binding sites in mouse kidney preparations with a displacement curve parallel to that for unlabeled dihydrotestosterone. Steroid receptor-mediated side effects, therefore, may not be confined to molecules with a common skeleton, such as steroids, spirolactones, and cardiac glycosides, but may extend to such apparently unrelated molecules as histamine antagonists and androgens.

Animals↗
PubMed1978

Investigation of cardiac beta-adrenoceptors using 125I-labelled 1-(4-iodophenoxy)-3-isopropylaminopropan-2-ol.

1-(4-iodophenoxy)-3-isopropylaminopropan-2-ol (IIP) is a potent beta-adrenergic antagonist which has been labelled to high specific activity with 125I and used to bind to rat myocardial membranes. The characteristics of binding were consistent with the known properties of beta-receptors. Thus, binding was highly stereospecific for the L-stereoisomer since L-propranolol was two orders of magnitude more potent than the D-isomer in competing for these sites. The beta-adrenergic agonists isoproterenol, epinephrine and norepinephrine competed for binding with potencies paralleling their pharmacological potencies as beta-adrenergic effectors. The dissociation constant for binding of IIP was 4--5 nM as measured either by direct binding studies or by its inhibition of isoproterenol stimulated adenylate cyclase. Binding was saturable with 0.06 pmoles of IIP per mg of membrane protein binding at saturation. 125IIP is a high affinity, high specific activity ligand suitable for use as a selective probe for the detection and quantitation of cardiac beta-receptors. Its introduction should help solve the problems involved in the investigation of myocardial beta-adrenergic receptors.

Adenylyl Cyclases↗