Biology Reference
In-Depth Information
Puberty, Stress and Kisspeptin
One major facet of reproductive research that concerns the effects of both kisspeptin
and stress is puberty. Characterized as the transition from juvenile to adult state of
reproductive development, growth, and adrenal maturation, pubertal timing in
mammals (including man) is controlled by a multiplicity of complex interactions
between genetic and environmental factors, with the latter providing fi ne tuning to
maximize reproductive potential to fi t the prevailing or predicted environment.
There is unequivocal evidence that chronic stress exposure suppresses the activity
of the HPG axis and delays puberty. However, less well recognized is the advance-
ment of puberty by environmental factors, such as psychosocial stress within the
family domain, including absence of father, as well as parental and mother-daughter
confl ict [ 12 ], with striking parallels in an animal model of weak parent-offspring
bonding [ 13 ]. The age at which girls are reaching puberty has been trending down-
wards in recent decades, coincident with the increasing prevalence of overweight
and obesity; this is in keeping with evidence that overnutrition advances puberty
[ 14 ] and body fatness and a rapid elevation in BMI are predictors of earlier onset of
puberty. However, recent studies reveal that this downward trend is evident irrespec-
tive of BMI, suggesting that other factors are involved [ 14 , 15 ]. Animal models of
delayed puberty (e.g., intrauterine growth retardation [ 16 , 17 ] or neonatal exposure
to LPS [ 18 ]) or advanced puberty (e.g., low maternal care [ 13 ] or high-fat diet [ 19 ])
also fail to show a clear correlation between body weight, body fat, or its central
signaling biomarker, leptin, and the timing of puberty.
Kisspeptin/Kiss1r signaling is a prerequisite for physiological development of
the reproductive system, since inactivating mutations in KISS1 [ 20 ] or KISS1R
[ 21 , 22 ] result in pubertal failure and hypogonadotropic hypogonadism in
humans. Kiss1 - and Kiss1r -knockout mouse models largely produce a similar
reproductive phenotype [ 23 - 25 ], although Kiss1 -knockdown results in a less
severe phenotype [ 26 ]. However, a recent report challenged the dogma that kiss-
peptin signaling is required for puberty and adult fertility in mice [ 27 ].
Nevertheless, levels of hypothalamic Kiss1 and Kiss1r expression peak at puberty
(Fig. 20.1 ) [ 18 , 28 , 29 ], and kisspeptin administration stimulates precocious
puberty in rats [ 30 ]. Furthermore, polymorphisms in the KISS1 gene [ 31 ] and
activating mutations in KISS1R [ 32 ] are associated with central precocious
puberty in humans. A variety of well-defi ned acute and chronic stress paradigms
and experimental parameters of pubertal development have facilitated in vivo
research aiming to elucidate the effects of stress on reproductive maturation.
However, to this end, few studies have directly addressed the involvement of kiss-
peptin in the alteration of pubertal dynamics in response to stress.
Exposure to an immune challenge, such as LPS, in the early neonatal period has
been shown to have profound and long-lasting effects on the stress response
throughout later life in the rat, evident through increased CRF gene expression in
the PVN of the hypothalamus and an increase in the pulse frequency and amplitude
of corticosterone (CORT) release [ 33 ]. We have shown that neonatal exposure to
Search WWH ::




Custom Search