Redirecting intracellular trafficking and the secretion pattern of FSH dramatically enhances ovarian function in mice

Although the two pituitary gonadotropins luteinizing hormone (LH) and FSH are synthesized in the same cell, gonadotrope, their intracellular trafficking and secretion pattern are distinct. LH is released as pulses via the regulated pathway, whereas FSH is constitutively secreted. Why this hormone-specific pattern has evolved and whether the target organ, the ovary, senses specific hormone release pattern is not understood. In this paper, a gonadotrope-specific sorting determinant on LH has been identified, and FSH was diverted into the LH secretory pathway in vivo. FSH released like LH from pituitary dramatically enhanced the ovarian responses. Our studies provide a molecular basis for the evolution of distinct patterns of gonadotropin secretion and explain the origin of estrus cycles in mammals.