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Regulation of Kisspeptin Synthesis and Release in the Preoptic/Anterior Hypothalamic Region of Prepubertal Female Rats: Actions of IGF ‐1 and Alcohol
Author(s) -
Hiney Jill K.,
Srivastava Vinod K.,
Vaden Anderson Danielle N.,
Hartzoge Nicole L.,
Dees William L.
Publication year - 2018
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.13539
Subject(s) - kisspeptin , medicine , endocrinology , receptor , preoptic area , hypothalamus , hypothalamic–pituitary–gonadal axis , chemistry , pi3k/akt/mtor pathway , hormone , insulin like growth factor , biology , luteinizing hormone , growth factor , signal transduction , biochemistry
Background Alcohol ( ALC ) causes suppressed secretion of prepubertal luteinizing hormone‐releasing hormone ( LHRH ). Insulin‐like growth factor‐1 ( IGF ‐1) and kisspeptin (Kp) are major regulators of LHRH and are critical for puberty. IGF ‐1 may be an upstream mediator of Kp in the preoptic area and rostral hypothalamic area ( POA / RHA ) of the rat brain, a region containing both Kp and LHRH neurons. We investigated the ability of IGF ‐1 to stimulate prepubertal Kp synthesis and release in POA / RHA , and the potential inhibitory effects of ALC . Methods Immature female rats were administered either ALC (3 g/kg) or water via gastric gavage at 0730 hours. At 0900 hours, both groups were subdivided where half received either saline or IGF ‐1 into the brain third ventricle. A second dose of ALC (2 g/kg) or water was administered at 1130 hours. Rats were killed 6 hours after injection and POA / RHA region collected. Results IGF ‐1 stimulated Kp, an action blocked by ALC . Upstream to Kp, IGF ‐1 receptor ( IGF ‐1R) activation, as demonstrated by the increase in insulin receptor substrate 1, resulted in activation of Akt, tuberous sclerosis 2, ras homologue enriched in brain, and mammalian target of rapamycin ( mTOR ). ALC blocked the central action of IGF ‐1 to induce their respective phosphorylation. IGF ‐1 specificity and ALC specificity for the Akt‐activated mTOR pathway were demonstrated by the absence of effects on PRAS 40. Furthermore, IGF ‐1 stimulated Kp release from POA / RHA incubated in vitro. Conclusions IGF ‐1 stimulates prepubertal Kp synthesis and release following activation of a mTOR signaling pathway, and ALC blocks this pathway at the level of IGF ‐1R.