A factor in cytosol enhances stimulation of membrane adenylate cyclase from human thyroid by thyrotrophin and thyroid stimulating immunoglobulins.
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Biomedical subjects
Publications and source records attributed to A Crawford.
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Plasma testosterone, serum FSH, and serum LH levels of 26 members of a club established for heterosexual transvestites were assayed. Mean plasma testosterone, serum FSH, and serum LH levels of the transvestite subjects were not significantly different from the normal range. The implications of these findings are discussed.
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FireMaster BP-6 is a commercial polybrominated biphenyl (PBB) preparation containing a complex mixture of isomers with the major component being identified as 2,2',4,4',5,5'-hexabromobiphenyl. Column chromatographic techniques have been developed in which the crude FireMaster is separated into three fractions, F1, F2, and F3, in increasing order of polarity. F1 consists of highly purified 2,2',4,4',5,5'-hexabromobiphenyl (94%) whereas F2-F3 contain less of this isomer and correspondingly more of the other bromobiphenyl components. Previously we have shown that crude FireMaster BP-6 is metabolized in mammals to give hydroxylated degradation products and the metabolism of F1, not unexpectedly, gives comparable results. It is well known that PBBs are effective inducers of diverse microsomal enzymes including including the aryl hydrocarbon hydroxylase (AHH) system. The effects of FireMaster BP-6 and F1-F3 as AHH inducers have been investigated by using the following approach: the substrates used to monitor AHH activity are model halogenated aromatic compounds; the levels of metabolites and metabolite conjugates formed have been quantitated for control and induced enzymes; the levels of macromolecular adducts have also been quantitated for the inducers. This approach thus not only measures the rate of increase of detoxification products (metabolites and metabolite conjugates) but also monitors the macromolecule adduct formation which represents a toxification route. The effects of the PBBs as AHH inducers will be discussed in terms of the above approach.
Adenylate cyclase activity in particulate fractions from a transplantable rat osteogenic sarcoma was stimulated in a dose-dependent manner by prostaglandins E1 and E2 (PGE1 and PGE2) and parathyroid hormone (PTH). Prostaglandin F2alpha was active at a high concentration (3 x 10(-4) mol/l). Pretreatment of membranes with collagenase plus hyaluronidase reduced the magnitude of the PTH effect but did not affect the size of the PGE1 effect. Guanosine 5'-triphosphate and its synthetic analogue 5'-guanylylimidodiphosphate (Gpp(NH)p) activated adenylate cyclase in particulate preparations from the osteogenic sarcoma. The latter agent produced much larger effects, although the concentrations required for half-maximal enzyme activation were the same for both agonists (approximately 2 x 10(-6) mol/l). The effects of PTH and Gpp(NH)p were supra-additive at some concentrations of hormone. The effects of PGE1 and Gpp(NH)p were supra-additive at all hormone concentrations tested. Pre-incubation of membrane particles for 6 min with PTH produced an enzyme activation which was not reversed by dilution through washing; pre-incubation with PGE1 did not produce this effect. The response of membrane adenylate cyclase to Gpp(NH)p (10(-4) mol/l) was 75% greater in preparations pre-incubated with PTH than in membranes pre-incubated in buffer alone or in buffer containing PGE1. The basal rate of cyclic AMP production in the adenylate cyclase assay system decreased over a 35 min incubation period. This decrease was prevented by addition of PTH or PGE1. Addition of NaF or Gpp(NH)p produced a steady increase in the rate of production of cyclic AMP with time. Membrane preparations did not reduce the biological activity of PTH and did not degrade 125I-labelled PTH. The results demonstrate that the PTH- and PGE-responsive adenylate cyclases of the osteogenic sarcoma have distinctly different properties and that particulate preparations of the tumour do not metabolize PTH.
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The aryl hydrocarbon hydroxylase activity for control, Aroclor 1254 and FireMaster BP-6 induced hepatic microsomes was determined using 4-chlorobiphenyl, a model PCB isomer, as the substrate. The assay system was used to quantitate the amount of metabolites, conjugates and macromolecular adducts formed for the induced and control microsomes. The metabolites and conjugates were designated detoxification (D) products and the macromolecular adducts designated as toxification (T) products. From the data it was then possible to determine a T/D index for each inducer and it is proposed that this index is useful in assessing the potential toxicity of microsomal enzyme inducers.
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