Interval required for gonadotropin-releasing hormone-agonist-induced down regulation of the pituitary in cynomolgus monkeys and duration of the refractory state.
OBJECTIVE
To determine the minimal interval of gonadotropin-releasing hormone agonist (GnRH-a) administration required to induce pituitary refractoriness to the positive feedback effects of estradiol (E2) and to determine the duration of the induced refractory state in a nonhuman primate model.


METHODS
Research laboratories of The Jones Institute for Reproductive Medicine.


METHODS
Cynomolgus monkeys with documented regular menstrual cycles.


METHODS
Part 1. Groups of four monkeys treated with leuprolide acetate (LA) for increasing intervals (0, 2, 4, 6, and 8 days), then challenged with E2 benzoate to induce a gonadotropin surge. Part 2. Groups of four monkeys treated with LA for the minimal time required to induce pituitary refractoriness (6 days), then challenged with E2 benzoate 2, 4, or 7 days after cessation of LA treatment.


METHODS
Pituitary luteinizing hormone and follicle-stimulating hormone and E2 levels were monitored.


RESULTS
A minimum of 5 days of treatment is required for LA to induce pituitary refractoriness to the positive feedback effects of E2 benzoate. Once the down regulated condition is achieved, the refractory state lasts for at least 4 but not more than 6 days.


CONCLUSIONS
The minimal treatment interval required for a GnRH-a to induce pituitary refractoriness to the positive feedback effects of estrogen and the duration of the induced refractory state are determined to be 5 days for these primates.
Winslow
K L
KL
Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk 23507.
Gordon
K
K
Williams
R F
RF
Hodgen
G D
GD
D000818:Animals; D004958:Estradiol / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D005246:Feedback; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D016729:Leuprolide / Q000008:administration & dosage* / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000097:blood; D008252:Macaca fascicularis; D010902:Pituitary Gland / Q000187:drug effects* / Q000502:physiology*
D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D016729:Leuprolide