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S J Brandes

Publications and source records attributed to S J Brandes.

4 recordsLinked to original sources
PubMed1990

IGF-I production by mouse osteoblasts.

Mouse osteoblasts contain and secrete insulinlike growth factor I (IGF-I), which can be measured by radioimmunoassay after separation from endogenous IGF-I binding activity. Our studies indicate that IGF-I is produced by all bone cell populations prepared by sequential digestion of mouse calvaria with collagenase and protease. Furthermore, relatively small amounts of IGF-I are cell associated, and IGF-I is recovered primarily in the cell medium after 24 h of culture. Basal IGF-I secretion is also density dependent, and secretion per cell is approximately 20-fold higher when cultures are inoculated at 0.125 versus 1.0 x 10(5) cells per cm2. Growth hormone increased the secretion of IGF-I only in cells released in the earlier stages of digestion. These growth hormone-responsive populations were previously shown to differ from late released cells in that they show a lower expression of the osteoblastic phenotype, harbor more EGF receptors per cell, and have a higher proliferative response to low doses of exogenous IGF-I and EGF. These data reaffirm the presence of different subclasses of bone cells in populations obtained by sequential digestion of bone and suggest that growth hormone stimulates IGF-I secretion by immature osteoblasts.

Animals↗
PubMed1988

Uptake of three [3H]progestins by target tissues in vivo: implications for the design of diagnostic imaging agents.

We have investigated the tissue distribution of radioactivity for 0.5-4 h following the i.v. injection of three tritium-labeled progestins in estrogen-primed, immature rats. Whereas [3H]progesterone shows minimal uterine uptake (less than 0.7% injected dose per gram; %ID/g), the two higher affinity, synthetic progestins [3H]R 5020 (promegestrone) and [3H]ORG 2058 show highly selective uptake that reaches 4-5% ID/g by 1-3 h. The uterus to non-target tissue activity ratio at 2-4 h is approximately 12-20 for R 5020 and ORG 2058, but less than 2 for progesterone; the uterus to blood activity ratio for R 5020 is also high (approximately 15), but is lower for ORG 2058, possibly due to the accumulation of radiolabeled metabolites in the blood. The uterine uptake is selectively blocked by simultaneous injection of a large dose of unlabeled steroid, indicating that the uptake is mediated by a high affinity, low capacity binding system, presumably the progesterone receptor. Pronounced uptake is also observed by the liver and into fat, but is not receptor-mediated. The highly selective target tissue uptake by the two synthetic steroids, but not by progesterone, indicates that one must have ligands with sufficiently high affinity for the target tissue receptor, as well as low affinity for certain non-receptor binding proteins, in order to obtain adequate contrast between target and non-target tissues in dynamic uptake studies. These guidelines will be important in the development of suitable in vivo imaging agents based on the progesterone receptor.

Animals↗
PubMed1987

Fluorinated androgens and progestins: molecular probes for androgen and progesterone receptors with potential use in positron emission tomography.

In order to develop imaging agents for receptor-positive tumors of the breast and prostate, we have investigated the binding affinity of several fluorine-substituted steroids in the testosterone and nortestosterone series for the androgen receptor and the progesterone receptor. The 6 alpha- and 11 beta-fluoro-, and 16 alpha-fluoroalkyl-substituted steroids were prepared by an olefin bromofluorination reaction followed by dehydrobromination or reductive debromination. The 17 alpha-fluoromethyl derivatives were prepared by fluoride ion attack on the 17-spiroepoxide or 17-spiro sulfate and the 17 alpha-fluoropropynyl derivative, by reaction of a propargyl alcohol precursor with diethylaminosulfur trifluoride. Of the compounds synthesized, 17 alpha-(3-fluoro-I-propynyl)nortestosterone was found to possess the highest binding affinity and selectivity for the progesterone receptor, and 11 beta-fluoronordihydrotestosterone had the greatest affinity for the androgen receptor. Both receptor systems seem to tolerate reasonably well the substitution of fluorine for hydrogen.

Androgens↗