Search

The marmoset adrenal is interesting as it is developmentally similar to humans and other primates, but in adulthood 17,20-lyase activity is very low. One possible explanation is an altered regulation of P450c17 expression by AT1-R. We investigated the expression and zonal distribution of the AT1-R in marmoset adrenal glands and adrenocortical cells in culture since it is known that AT1-R is a regulator of P450c17 expression and activity. AT1-R was expressed strongly in the ZG and to diminishing degrees through the remainder of the cortex. There was negative expression in a putative ZI. Dispersed adrenocortical cells retained AT1-R protein as detected by ICC. Cells cultured for several days and treated in serum-free media for 48 h maintained AT1-R expression, as measured by western. However, at that 48 h time point, treatment with Forsk, AII, TPA, or the combination of A + F or T + F did not appear to effect AT1-R expression. We conclude that marmoset adrenals express AT1-R similarly to humans and other higher mammals, adrenocortical cells retain AT1-R expression in culture, and consistent with other adrenal cell culture models, AT1-R expression is not lost in response to agonists long term. [ABSTRACT FROM AUTHOR]

Discusses topics and issues about receptors and signal transduction. Insights into the role of exercise in bypassing the morbid effects of MC4R knockout in mice models; Elucidation on the use of modern protein and cloning technology to address the issue of the function of the now cloned MC2R receptor; Discussion on issues of fatty acid metabolites in the control of steroidogenesis.

Marmosets express a fetal zone during adrenal development but fail to produce significant amounts of C19 steroids in adulthood. It is not clear however if P450c17 regulation is different from that in humans/rhesus or the primary sequence is altered. To this end we isolated marmoset and rhesus adrenocortical cells, and treated the cells with known regulators of P450c17 expression for 48 h. P450c17 protein increased with Forskolin(F) treatment, but was marginally inhibited by AII(A) and TPA(T) alone. Combined A + F and T + F dramatically ablated the F response. Cortisol levels(EIA) increased upon F treatment and were inhibited by A and T. Combination of treatments partially inhibited the F-induced response. The protein-coding region of marmoset and rhesus P450c17 cDNAs were then isolated from adrenals using RT-PCR/TA cloning. Marmoset P450c17 shows one amino acid deletion but otherwise shares 90.6% and 91.4% homologies with the human and rhesus cDNA sequences, and 82.4% and 85% homologies with the human and rhesus predicted AA sequences, respectively. Since marmoset adrenocortical cells exhibit similar endocrine function to rhesus, impaired 17,20-lyase activity in the adult marmoset adrenal may in part be due to differences in the primary sequence. [ABSTRACT FROM AUTHOR]