PERIPHERAL-TYPE BENZODIAZEPINE RECEPTOR LIGANDS AND SERUM STEROID-HORMONES

The peripheral-type benzodiazepine receptors (PER) are involved in var ious cellular functions, including steroidogenesis. The impact of thes e receptor ligands has been demonstrated mainly in steroidogenic cells . The aim of the present study was to assess in intact female rats the effect of chronic (21 days) administration of the PER ligands PK 1119 5 (15 mg/kg) and Ro 5-4864 (5 mg/kg), the mixed ligand diazepam (5 mg/ kg), and the central benzodiazepine receptor ligand clonazepam (1 mg/k g) on PER binding characteristics in steroidogenic (ovary and adrenal) and non-steroidogenic (uterus and kidney) organs, as well as on serum hormonal steroids (estradiol, progesterone, and corticosterone). Sele ctive and mixed PER Ligands up-regulated PER density in the two steroi dogenic organs, while Ro 5-4864 also induced elevation of the receptor density in the non-steroidogenic organs. In contrast to Ro 5-4864, PK 11195 treatment down-regulated renal PER. Clonazepam elevated adrenal PER. On the serum hormonal level, Ro 5-4864 suppressed estradiol secr etion. The other ligands did not affect hormonal steroid levels. It ap pears that in female rats, at least at these doses and dosing schedule s, there is no correlation between the impact of chronic in vivo expos ure to these agents on PER density and ovarian and adrenal hormone lev els. (C) 1997 Elsevier Science B.V.