Endocrinology, Vol 120, 1000-1009, Copyright © 1987 by Endocrine Society

ARTICLES

Augmented transport and metabolism of sex steroids in lymphoid neoplasia in the rat

WT Cefalu and WM Pardridge

Sex steroid hormones have been shown to influence a number of biological properties of lymphoid neoplastic tissue. Since receptor occupancy is a function of the pool size of cellular exchangeable hormone, it is important to understand the mechanisms regulating hormone transport from the microcirculation and hormone metabolism, since these two pathways are the dominant factors controlling cellular exchangeable hormone. In the present studies, steroid hormone transport and metabolism were investigated in control and neoplastic lymph nodes after transplanting control rats with the WR-6 leukemic line. Steroid hormone transport and metabolism were studied after pulse labeling the nodal tissue in vivo with arterial bolus injections of [3H]testosterone. Residual vascular radioactivity was monitored by simultaneously injecting 113mindium chelated to bovine transferrin. Both testosterone and estradiol were partially available for transport through the capillary barriers of control and neoplastic lymph nodes from the circulating albumin-bound pool. Estradiol was readily available for transport from the circulating sex hormone-binding globulin-bound pool in both control and neoplastic lymph nodes. Testosterone was not available for transport from the sex hormone- binding globulin-bound pool in control lymph nodes, but was readily available for transport in metastatic lymph nodes. Thaw-mount autoradiography and physiological measurements showed that plasma proteins such as albumin or transferrin were confined to the microcirculation compartment. Therefore, the transport of protein-bound hormones into lymph node represents a mechanism of enhanced steroid hormone dissociation from the binding protein without the plasma protein per se significantly exiting the microcirculation compartment. Metabolic studies showed no measurable metabolism of [3H]testosterone in the control lymph nodes by 60 sec after arterial injection. However, testosterone was extensively metabolized in metastatic lymph nodes; the major metabolites formed from testosterone comigrated on a two- dimensional TLC system with epiandrosterone/androsterone and dihydrotestosterone. In conclusion, these studies indicate that both steroid hormone transport and metabolism are augmented in the lymphoid neoplastic state, and both processes may alter the concentration of cellular exchangeable hormone and, thus, steroid hormone receptor occupancy in lymphoid neoplasms.