Upregulation of GH, but not IGF1, in the hippocampus of the lactating dam after kainic acid injury

Abstract

Lactation embodies a natural model of morphological, neurochemical, and functional brain plasticity. In this reproductive stage, the hippocampus of the female is less sensitive to excitotoxins in contrast to nulliparity. Growth hormone (GH) and insulin-like growth factor 1 (IGF1) are known to be neuroprotective in several experimental models of brain lesion. Here, activation of the GH–IGF1 pituitary–brain axis following kainic acid (7.5 mg/kg i.p. KA) lesion was studied in lactating and nulliparous rats. Serum concentrations of GH and IGF1 were uncoupled in lactation. Compared to virgin rats, the basal concentration of GH increased up to 40% but IGF1 decreased 58% in dams, and only GH increased further after KA treatment. In the hippocampus, basal expression of GH mRNA was higher (2.8-fold) in lactating rats than in virgin rats. GH mRNA expression in lactating rats increased further after KA administration in the hippocampus and in the hypothalamus, in parallel to GH protein concentration in the hippocampus of KA-treated lactating rats (43% vs lactating control), as detected by Western blot and immunofluorescence. Except for the significantly lower mRNA concentration in the liver of lactating rats, IGF1 expression was not altered by the reproductive condition or by KA treatment in the hippocampus and hypothalamus. Present results indicate upregulation of GH expression in the hippocampus after an excitotoxic lesion, suggesting paracrine/autocrine actions of GH as a factor underlying neuroprotection in the brain of the lactating dam. Since no induction of IGF1 was detected, present data suggest a direct action of GH.

Neuroprotective Effects of Growth Hormone (GH) and Insulin-Like Growth Factor Type 1 (IGF-1) after Hypoxic-Ischemic Injury in Chicken Cerebellar Cell Cultures

“…Our results showed that this hormonal system increases its local expression in response to cell damage, mainly during reoxygenation, although it is important to note that GHR expression decreases in this condition, perhaps as a negative feedback mechanism. These results are consistent with the numerous evidence that indicates that the endogenous expression of GH and IGF-1 during a damaging condition, whether due to hypoxia [11,61], excitotoxicity [12,62], or trauma [13,63], plays a critical role within the mechanisms triggered by neurons to preserve their survival and viability.…”

Growth Hormone (GH) and Gonadotropin-Releasing Hormone (GnRH) in the Central Nervous System: A Potential Neurological Combinatory Therapy?

“…The neuroprotective actions of GH in the hippocampus include prevention of excitotoxic cell death [ 106 ]. In lactating rats treated with kainic acid, hippocampal GH increased significantly, demonstrating a locally mediated neuroprotection mechanism [ 107 ]. It has been shown that damage due to oxidative stress, neurotoxicity, or hypoxic injury was reduced in GH-treated subjects, suggesting that this effect likely involves both local and systemic IGF-I actions [ 108 , 109 , 110 ].…”

Physiological changes of growth hormone during lactation in pup rats artificially reared

“…For the Gh , the primer used was developed by Dra. Maricela Luna [38]: Forward ; Reverse . The following pre-developed assays from Life Technologies were used: for rat Igf 1, the assay Rn00710306_m1, for Gapdh , which was used as a constitutive gene for Igf1 , the assay Rn01775763_g1.…”