TY - JOUR
T1 - Reproductive hormone levels after pituitary allograft in cyclosporin-treated monkeys
AU - Bethea, C. L.
AU - Hess, D. L.
AU - Ronnekleiv, O.
AU - Freesh, F.
N1 - Funding Information:
Received February 18, 1991; revised and accepted June 20, 1991. * Publication no. 1792 of the Oregon Regional Primate Research Center. t Supported by the National Institutes of Health, Bethesda, Maryland through a National Institute of Child Health and Human Development grant HD17265 to CLB and the Population Center P30 program project grant HD18185, and through the Animal Resources Branch grant RR00163 for operation of the Oregon Regional Primate Research Center.
PY - 1991
Y1 - 1991
N2 - 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. Design: 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. Setting: Oregon Regional Primate Research Center, Beaverton, Oregon. Participants: Female Macaca mulatta exhibiting regular menstruation. Interventions: None. Main Outcome Measures: 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. Conclusion: 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.
AB - 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. Design: 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. Setting: Oregon Regional Primate Research Center, Beaverton, Oregon. Participants: Female Macaca mulatta exhibiting regular menstruation. Interventions: None. Main Outcome Measures: 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. Conclusion: 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.
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U2 - 10.1016/S0015-0282(16)54611-1
DO - 10.1016/S0015-0282(16)54611-1
M3 - Article
C2 - 1915954
AN - SCOPUS:0026047268
SN - 0015-0282
VL - 56
SP - 754
EP - 763
JO - Fertility and sterility
JF - Fertility and sterility
IS - 4
ER -