Invited review: Interactions between prolactin and local regulation of the mammary gland

Biological mechanisms exist to adjust milk output to demand. Experiments where different milking frequencies were used within the mammary gland have shown that milk production is only increased in the frequently milked half during a unilateral increase in milk frequency. Similarly, cessation of milking or mastitis of one quarter will induce the involution process in that quarter only. These data strongly suggest that milk production is regulated at the level of the mammary gland. However, other factors, such as pregnancy, bST administration, and photoperiod, also indicate the presence of a systemic regulation of milk secretion. Moreover, the linkages between local and systemic regulations are poorly understood. We have identified 3 potential links between local and systemic regulation: milking and suckling inducing the release of hormones; modulation of the receptivity of the mammary gland to the systemic lactogenic signal; and secretion in milk of inhibitory substances that modulate response to systemic regulation. Therefore, a series of experiments was initiated to examine these potential linkages between local and systemic regulations. A first experiment provided no evidence that additional milking-induced hormone release episodes contribute to the stimulating effect of increasing milking frequency during an established lactation. Conversely, we found evidence that both milking frequency and incomplete milking modulate mammary gland responsiveness to prolactin, and this is likely to contribute to their milk production response. We also found that the circulating level of prolactin affects the subsequent responsiveness to this hormone and that it is likely involved in the reduction of milk production after a short dry period. Finally, using an animal model that is unaffected by an inflammatory response, we found indications supporting the contention that milk stasis leads to the accumulation of one or more factors that trigger involution. Additionally, we determined that the milk levels of several microRNAs are affected by milk stasis and deserve further research to understand their roles in the control of mammary gland functions.