Non-metabolic and metabolic factors causing lactational anestrus: rat models uncovering the neuroendocrine mechanism underlying the suckling-induced changes in the mother.

Follicular development and ovulation are strongly inhibited during lactation. Administration of a high dose of estrogen induces luteinizing hormone (LH) surges in ovariectomized lactating rats, suggesting that brain mechanisms regulating cyclic LH release remain intact in lactating mothers. On the other hand, tonic LH release is profoundly suppressed in lactating rats. This suggests that lactational anestrus is mainly due to suppression of the mechanism regulating pulsatile gonadotropin-releasing hormone secretion in the hypothalamus, which is responsible for follicular development and steroid production. Both metabolic and non-metabolic factors are involved in suppressing pulsatile LH secretion throughout lactation in rats. During the first half of lactation, pulsatile LH secretion is strongly suppressed, even if milk production is attenuated by pharmacological blockade of prolactin secretion in ovariectomized lactating rats. Pulsatile LH release quickly recovers by removing pups or blocking neuronal input by hypothalamic deafferentation during the period. These data suggest that the suckling stimulus itself is responsible for suppression of LH release during the first half of lactation. During the second half of lactation, negative energy balance, which is caused by the milk production, appears to play a dominant role in suppressing LH secretion. Blockade of milk production by inhibiting prolactin release causes a gradual increase in LH release even if the vigorous suckling stimulus by foster pups remains. In conclusion, the suckling stimulus itself predominantly suppresses LH pulses during the first half of lactation and metabolic factors take over the role of the suckling stimulus during the second half of lactation.