Fadrozole

Cell lines

Prolactin-positive cells

Preparation Method

Male Wistar rats (175–200g) were killed to extract prolactin-positive cells. Prolactin-positive cells were seeded on 60 culture chamber slides at a final concertation of 2.5×10⁵/ml cells and incubated with Dulbecco’s modified Eagle’s medium (DMEM) for 7 days. On day 4, medium was changed by fresh DMEM. On day 7, cell cultures were treated with 1μM testosterone, 1μM Fadrozole and incubated for 1, 3, 6 or 12 hours (5 chambers per treatment). After treatment, the chambers were washed with Dubelcco’s sterile PBS, and cells were fixed in Somogy’s solution for 1 hour, followed by rinsing in PBS.

Reaction Conditions

1μM testosterone, 1μM Fadrozole; 1, 3, 6 or 12 hours

Applications

Fadrozole alone did not affect prolactin-positive cells. Combination of Fadrozole and testosterone significantly decreases prolactin-positive cells sizes and proliferation rates.

Animal models

Sprague–Dawley female rats

Preparation Method

Female rats (180-300g) were mated when 60-120 days old. On day 14 of pregnancy rats were divided into three groups. Group 1 (Fad) rats were implanted s.c. with mini-osmotic pumps containing Fadrozole (300μg/day). Group 2 (control) rats were implanted s.c. with mini-osmotic pumps containing saline. Group 3 (Fad+E₂) rats were implanted s.c. with mini-osmotic pumps containing Fadrozole (300μg/day) and estradiol-17 (E₂) (0.2μg/day, E₂ was dissolved in 0.2ml sesame oil). On day 17 of pregnancy, blood samples were collected from the abdominal aorta of rats in all 3 groups. On day 20 of pregnancy, all 3 groups rats underwent laparotomy under ether anesthesia.

Dosage form

Fadrozole: 300μg/day for 6 days; estradiol-17: 0.2μg/day for 6 days

Applications

Fadrozole treatment significantly reduced E₂ concentration, and led to a fourfold increased intrauterine pressure with smaller uterine tissue framework in pregnant rats. Fadrozole caused fetal abnormalities in pregnant rats, but their weight did not differ from normal fetuses. The combination treatment of Fadrozole and E₂ had similar effect as control groups, indicating that exogenously supplied E₂ could compensate for the loss of endogenous E₂.

References:
[1] Patil CN, Li W, Wang X. Local transformations of androgens into estradiol by aromatase P450 are involved in the regulation of prolactin and the proliferation of pituitary prolactin-positive cells. J Endocrinol. 2014;222(2):201–12. doi:10.1530/JOE-13-0579.
[2] Tamada H, Shimizu Y, Inaba T, Kawate N, Sawada T. The effects of the aromatase inhibitor fadrozole hydrochloride on fetuses and uteri in late pregnant rats. Journal of endocrinology. 2004 Feb 1;180(2):337-46.