Reproductive hormone levels after pituitary allograft in cyclosporin-treated monkeys.
OBJECTIVE
To determine the course of events during the onset of hyperprolactinemic amenorrhea, a nonhuman primate model was sought that did not require suckling or interference with the in situ hypothalamic-pituitary axis.


METHODS
Because removal of the adenohypophysis from hypothalamic influence results in secretion of large quantities of prolactin (PRL) but little of the other adenohypophyseal hormones, we explored the possibility of establishing pituitary allografts in monkeys. Normally cycling female rhesus monkeys were immunosuppressed with a daily regimen of cyclosporin A (CyA; 10 to 15 mg/kg per day) and then subcutaneously grafted with a pituitary from another animal (allograft). Blood samples were obtained daily via saphenous vein puncture during control, only CyA-treatment, and allografted-plus CyA- menstrual cycles.


METHODS
Oregon Regional Primate Research Center, Beaverton, Oregon.


METHODS
Female Macaca mulatta exhibiting regular menstruation.


METHODS
None.


METHODS
Prolactin, luteinizing hormone (LH), estradiol (E2), and progesterone (P) levels were determined in harvested serum.


RESULTS
Temporary survival of 5 of 11 (45%) allografts was assumed based on elevations in serum PRL. Of the viable grafts, 4 of 5 (80%) resulted in reproductive dysfunction, as first evidenced by delay or loss of the preovulatory rise in E2. When the peak of follicular E2 was delayed, then the LH surge occurred, but it was also delayed. If follicular E2 levels did not peak, then the LH surge was absent as was luteal P production.


CONCLUSIONS
These data suggest that in the etiology of PRL-induced infertility in women, the first event is a suppression of follicular E2 production. In addition, the hypothalamus probably remains responsive to the positive feedback of E2 during early or moderate hyperprolactinemia.
Bethea
C L
CL
Oregon Regional Primate Research Center, Beaverton 97006.
Hess
D L
DL
Ronnekleiv
O
O
Freesh
F
F
D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D004958:Estradiol / Q000097:blood*; D005260:Female; D006085:Graft Survival; D007986:Luteinizing Hormone / Q000097:blood*; D008253:Macaca mulatta; D010902:Pituitary Gland / Q000637:transplantation*; D011374:Progesterone / Q000097:blood*
D011374:Progesterone; D004958:Estradiol; D016572:Cyclosporine; D007986:Luteinizing Hormone