Abortifacient Effects in the Pregnant Hamster of an Antibody to Progesterone are Reversed by Exogenous Prolactin1
| Autor: | Gilbert S. Greenwald, Ming-Wei Wang |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
endocrine system
medicine.medical_specialty Pregnancy Uterus Hamster Cell Biology General Medicine Biology medicine.disease Prolactin medicine.anatomical_structure Endocrinology Reproductive Medicine Internal medicine Follicular phase Luteolysis medicine biology.protein Antibody hormones hormone substitutes and hormone antagonists Abortifacient |
| Zdroj: | Biology of Reproduction. 51:504-508 |
| ISSN: | 1529-7268 0006-3363 |
| DOI: | 10.1095/biolreprod51.3.504 |
| Popis: | A single i.p. injection of 10 nmol of a monoclonal antibody to progesterone (mAb-P4 ) on Day 4 of pregnancy (day of nidation) interrupts pregnancy by Day 8 (Day 1 = sperm-positive smear) in 75% of treated hamsters (n = 8). This correlates with structural and functional luteolysis, significantly (p < 0.05) reduced serum prolactin (PRL), and a nonsignificant trend for reduced FSH (which constitute the minimal luteotropic complex of the hamster), but LH is unchanged. Embryos implant and develop normally for a while, but by Day 8 the uterus is distended with the resorbing products of conception. The abortifacient effects of passive immunization against progesterone are reversed 100% by s.c. injection of 100 jtg PRL daily on Days 4-7; deferring PRL treatment until Days 6-7 maintained pregnancy in 75% of the animals, still significantly different from the untreated mAb-P4 group. Injection of 50 jlg PRL on Days 4-7 maintains pregnancy in 50% of the mAb-P4-treated hamsters (not significantly different), whereas 10 jLg PRL on Days 4-7 is wholly ineffective. No dose of FSH (0.1-10.0 tIg) or LH (0.4-2.0 jig) on Days 4-7 reversed the effects of mAb-P4 ; neither did 10 jig PRL plus 0.4 or 2 jLg of FSH. The maintenance of.pregnancy after 100 RIg PRL on Days 4-7 is associated with normal serum levels of PRL, FSH, and LH and no change in the serum concentration of the mAb-P4 antibody. The fall in serum FSH after injection of mAb-P4 is the result of accelerated follicular growth at the onset of luteolysis; the follicles in vitro secrete progressively higher levels of inhibin on Days 6, 7, and 8 of pregnancy. Thus, the trend for the decline in FSH is most likely a secondary event. The primary event therefore appears to be disruption of a positive feedback loop of the hypothalamic-pituitary-ovarian axis. As free (non-antibody bound) P4 drops to undetectable levels, PRL secretion is lowered, and one of the principal luteotropins is withdrawn. In this animal model, mAb-P4 therefore does not act directly at the uterine level. |
| Databáze: | OpenAIRE |
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