Servomechanism of prolactin and progesterone in regulating uterine gene expression

Abstract

To investigate the interaction of PRL and progester-one in regulating uterine gene expression, we have quantitated the concentration of PRL receptor and of uteroglobin (UG) mRNA in the endometrium of rabbits of different ages and after treatment with different hormones. During uterine differentiation in 2- to 4-week old rabbits, a marked increase in un-occupied uterine PRL receptor number was ob-served, presumably increasing uterine sensitivity to PRL. Receptor values for 4-week old rabbits were comparable to values for sexually mature, estrous females, but were lower than in 5-day pseudopreg-nant (PSP) animals. When total PRL receptor was determined by Scatchard analysis after in vitro de-saturation with MgCl2, PSP animals again expressed the highest receptor concentration with no changes in the dissociation constant (Kd) values. To deter-mine whether progesterone regulates uterine PRL receptor, long term ovariectomized rabbits (>12 weeks) were treated with various combinations of hormones, and unoccupied and total uterine PRL receptors were determined. Progesterone treatment resulted in the highest concentration of both unoc-cupied and total PRL receptor after desaturation and removal of anti-ovine PRL antibodies with MgCl2. The value for total uterine PRL receptor was equiv-alent to the value for mammary gland, and the Kd values (2-4 × 10-10 m) were similar. Treatment of long term ovariectomized rabbits with progesterone, with or without estradiol, produced an increase (P < 0.05) in the UG mRNA content, which also occurred in PSP animals. PRL alone had no effect on UG mRNA but PRL plus progesterone increased (P < 0.05) UG mRNA in a dose-dependent manner. We propose a servomechanism by which PRL acts mor-phologically and biochemically to enhance the uter-ine response to progesterone. © 1988 by The Endocrine Society.