Does salt have a permissive role in the induction of puberty?

Abstract

Puberty is starting earlier than ever before and there are serious physiological and sociological implications as a result of this development. Current research has focused on the potential role of high caloric, and commensurate high adiposity, contributions to early puberty. However, girls with normal BMI also appear to be initiating puberty earlier. Westernized diets, in addition to being high in fat and sugar, are also high in salt. To date, no research has investigated a link between elevated salt and the reproductive axis. We hypothesize that a high salt diet can result in an earlier onset of puberty through three mechanisms that are not mutually exclusive. (1) High salt activates neurokinin B, a hormone that is involved in both the reproductive axis and salt regulation, and this induces kisspeptin release and ultimate activation of the reproductive axis. (2) Vasopressin released in response to high salt acts on vasopressin receptors expressed on kisspeptin neurons in the anteroventral periventricular nucleus, thereby stimulating gonadotropin releasing hormone and subsequently luteinizing hormone secretion. (3) Salt induces metabolic changes that affect the reproductive axis. Specifically, salt acts indirectly to modulate adiposity, ties in with the obesity epidemic, and further compounds the pathologic effects of obesity. Our overall hypothesis offers an additional cause behind the induction of puberty and provides testable postulates to determine the mechanism of potential salt-mediated affects on puberty.

Fig. 1

Schematic of the Salt-Puberty hypothesis illustrating 3 different, but not mutually exclusive, physiological pathways through which salt may affect puberty. (1) Salt activates KNDy neurons by stimulating release of NKB, either from KNDy neurons or local NKB neurons. NKB binds to NK₃R leading to kisspeptin release which activates GPR54 receptors on GnRH neurons. (2) Salt stimulates release of vasopressin into 3rd ventricle, which activates its receptor, V1aR, on kisspeptin neurons in the AVPV that activate GnRH neurons. (3) Adipoctye released adipokines (e.g. leptin) which activate adipokine receptors. Adipokine receptor expressing neurons either directly or indirectly contact KNDy neurons to drive the effects of salt on puberty.