Interaction between luteinizing hormone and prolactin receptors in the rat ovary

The loss of luteotropic receptors for prolactin (PRL) and luteinizing (LH) hormone in the rat corpus luteum under desensitizing conditions suggests a mechanism designed to reduce target cell responsiveness to excessive hormone stimulation. The mechanism involved in the coordinated loss of both receptors during down regulation is unknown but may involve cointernalization of LH and PRL receptors within the same endocytic vesicle. This may imply that a close physical association exists between luteotropic receptors in the rat corpus luteum. The present studies examine the kinetics and pattern of PRL and LH receptor loss and recovery in the corpus luteum of PMSG/hCG primed immature rats. Seven days after PMSG treatment rats were injected with either hCG, GnRH or PGF_2a and sacrificed at selected time points over a period of 8 days, A desensitizing dose (6-9µg) of hCG caused a 70-80% decrease in LH receptors within 24 hours. LH receptor levels remained low until day 2 but recovered to (or above 50%) control values by day 4, GnRH (2µg des Gly¹⁰,[0-Ala6]GnRH ethylamide) caused LH receptors to decrease 40-50% by day 1 from which final receptor numbers slowly increased to peak levels at days 4 and 6, PGF_2a (1 and 2mg Lutalyse) caused LH receptors to decrease more slowly compared to hCG treatment. However, LH receptors continued to decrease and remained well below control values for the entire 8 day period. By contrast, the loss of lactogen receptors occurred as early as 6 hours after treatment with hCG, GnRH 1 V or PGF_2a. This was followed by a faster recovery when compared to LH receptors. These results indicate a similarity in loss and recovery of PRL and LH receptors in the rat corpus luteum. The association between LH and PRL receptors was further investigated by adding fluorescein-hCG and rhodamine-oPRL to cultures of rat granulosalutein cells and incubating at either 15 minutes or 2 hours at 37°C. Fluorescence from both fluorescein and rhodamine was localized as distinct patches in close proximity to each other on the surface and intracellularly. These results suggest that receptors for LH and PRL are functionally coupled and that during periods of continued hormonal stimulation, both receptors are internalized within the same endocytic vesicle.