Endocrine and antitumoral effects of R76713 in rats.
Some effects of daily oral administration of a new non-steroidal aromatase inhibitor on the pituitary-gonadal and adrenal functions were investigated in female rats. At doses of 1 mg/kg twice daily or higher, R 76713 lowered plasma estradiol levels to the range measured after ovariectomy Plasma progesterone levels and uterine weights decreased whilst LH levels increased but to a lesser extent than after ovariectomy. The other hormonal data show that long-term administration of R 76 713 does not modify the gluco- and mineralocorticoid hormone levels even at the highest dose studied (20 mg/kg, 4 h after treatment). Furthermore, both ovariectomy and R 76 713 treatment (1 and 5 mg/kg twice a day) induced almost complete regression of 9,12-dimethyl-1,2-benzanthracene-induced mammary carcinoma in rats. The appearance of new tumors during the treatment period was completely inhibited by R 76 713 whilst multiplicity of the remaining tumors was dramatically reduced.
De Coster
R
R
Department of Endocrinology and Oncology, Janssen Research Foundation, Beerse, Belgium.
Van Ginckel
R
R
Wouters
W
W
Goeminne
N
N
Vanherck
W
W
Byloos
M
M
D000305:Adrenal Cortex Hormones / Q000097:blood; D000311:Adrenal Glands / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D047072:Aromatase Inhibitors; D001835:Body Weight / Q000187:drug effects; D004958:Estradiol / Q000097:blood; D005260:Female; D007986:Luteinizing Hormone / Q000097:blood; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D010053:Ovary / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D011374:Progesterone / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D014230:Triazoles / Q000494:pharmacology* / Q000627:therapeutic use; D014599:Uterus / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*
D000305:Adrenal Cortex Hormones; D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D014230:Triazoles; C060523:vorozole; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone