Loss of luteal sensitivity to luteinizing hormone underlies luteolysis in cattle: A hypothesis.

By virtue of the secretion of progesterone (P4), corpus luteum (CL) is important not only for normal cyclicity but also for conception and continuation of pregnancy in female mammals. Luteolysis (also called luteal regression) is defined as loss of the capacity to synthesize and secrete P4 followed by the demise of the CL. There is strong evidence that sequential pulses of prostaglandin F2α (PGF) secreted from the uterus near the end of luteal phase induces luteolysis in farm animals. Loss of luteal sensitivity to luteinizing hormone (LH) at the end of menstrual cycle has been reported to be critical for initiation of luteolysis in primates, however this has not been investigated in farm animals. A closer observation of the published real-time profiles of circulating hormones (P4, LH, and PGF) and their inter-relationships around the time of the beginning of spontaneous luteolysis in cattle revealed- 1) A natural pulse of PGF causes a transient P4 suppression lasting a couple of hours followed by a rebound in P4 concentration, 2) The P4 secretions that occur in response to LH pulses before the beginning of luteolysis (i.e., preluteolysis) either fail or do so to a lesser extent during luteolysis indicating a loss of sensitivity to LH, and 3) The loss of sensitivity coincides with the beginning of luteolysis (i.e., transition), and apparently luteolysis does not initiate until there is loss of sensitivity to LH. The CL is sensitive to LH during preluteolysis, and the LH-stimulated P4-dependent and/or independent local survival mechanisms maintain the steroidogenic capability and viability of the CL until the very end of preluteolysis. Luteolysis does not appear to initiate with the PGF pulse(s) that occur during this period. With the loss of sensitivity to LH at the transition, however, a progressive decline in P4 begins initiating luteolysis. Also, the survival mechanisms become compromised making the CL less viable. The uterine PGF pulses that occur after the beginning of luteolysis induces increase in the local luteolytic factors, which contribute to further luteolysis, more importantly, structural luteolysis with ultimate demise of the CL. Therefore, I hypothesize that the loss of luteal sensitivity to LH underlies luteolysis in cattle. The hypothesis not only unifies the basic mechanism of luteolysis in a farm animal and primates but also provides a perspective to view luteolysis as a process rather than a factor-mediated event. A novel unified working model for luteolysis in a farm animal and primates is described. A better understanding of the luteal physiology including how responsiveness to LH diminishes in aging CL would help in the development of novel strategies in modulating CL structure-function to improve and/or control fertility in humans as well as in animals.