Specific binding of luteinizing hormone to leydig tumor cells

A radioimmunoassay was used to detect luteinizing hormone (LH) bound to washed Leydig tumor cells. Tumor cell suspensions were incubated with LH at 37° and washed repeatedly by centrifugation with isotonic 0.9% NaCl solution. The tumor cells contained large quantities of LH even after they were washed sufficiently to produce a 106-fold dilution of unbound LH. Six washings (106-fold dilution) were no more effective in removing LH from the cells than three washings (103-fold dilution). Binding was not influenced by the temperature at which the cells were washed. The extent of LH binding was related to the number of cells, with approximately 5300 ± 960 molecules of LH bound per cell. LH binding was also proportional to the same concentrations of LH which produced a steroidogenic dose response curve. The binding constant of 1.5 × 10-8 m was considered to be higher than that expected for nontumorous tissues. Tumor cells bound more LH than did erythrocytes or thymocytes under the same conditions

Cessation of steroidogenesis in leydig cell tumors after removal of luteinizing hormone and adenosine cyclic 3',5'-monophosphate

Luteinizing hormone (LH), but not follicle-stimulating hormone or prolactin, was shown to enhance steroid synthesis of Leydig tumor cells in vitro. Adenosine cyclic 3',5'-monophosphate (cAMP) duplicated the effect of LH. Removal of LH from the medium within 1 hour of incubation by washing the cells had no effect on the rate of steroid synthesis previously stimulated by LH. Under these conditions, addition of LH antiserum was required to reduce steroid synthesis. In contrast, removal of cAMP by washing the tumor cells caused a rapid termination of the previously induced steroidogenesis. Cycloheximide reduced the steroid synthesis initiated by LH. These results suggest that (a) steroidogenesis may be controlled by short lived factors (proteins), (b) LH may be required continually to elevate cAMP levels to maintain steroid synthesis at stimulated rates, and (c) that LH is probably bound to the tumor cells

Bone loss and the aromatase inhibitors

The increasing use of systemic adjuvant therapies has considerably improved the prognosis from early breast cancer. However, some of these therapies affect bone metabolism, resulting in osteoporosis. Aromatase inhibitors lower circulating oestrogen levels to almost unrecordable levels in postmenopausal women, predisposing them to bone loss with an increase in fracture risk. Ongoing clinical trials are favouring the use of the aromatase inhibitors over tamoxifen and this may advocate greater use of these drugs in the future. Strategies for the identification and management of treatment-induced bone loss are currently being defined