Abstract
Humanin (HN) is a 24-amino acid peptide with cytoprotective action in several cell types such as neurons and testicular germ cells. Rattin (HNr), a homologous peptide of HN expressed in several adult rat tissues, also has antiapoptotic action. In the present work, we demonstrated by immunocytochemical analysis and flow cytometry the expression of HNr in the anterior pituitary of female and male adult rats as well as in pituitary tumor GH3 cells. HNr was localized in lactotropes and somatotropes. The expression of HNr was lower in females than in males, and was inhibited by estrogens in pituitary cells from both ovariectomized female and orquidectomized male rats. However, the expression of HNr in pituitary tumor cells was not regulated by estrogens. We also evaluated HN action on the proapoptotic effect of TNF-α in anterior pituitary cells assessed by the TUNEL method. HN (5 µM) per se did not modify basal apoptosis of anterior pituitary cells but completely blocked the proapoptotic effect of TNF-α in total anterior pituitary cells, lactotropes and somatotropes from both female and male rats. Also, HN inhibited the apoptotic effect of TNF-α on pituitary tumor cells. In summary, our results demonstrate that HNr is present in the anterior pituitary gland, its expression showing sexual dimorphism, which suggests that gonadal steroids may be involved in the regulation of HNr expression in this gland. Antiapoptotic action of HN in anterior pituitary cells suggests that this peptide could be involved in the homeostasis of this gland. HNr is present and functional in GH3 cells, but it lacks regulation by estrogens, suggesting that HN could participate in the pathogenesis of pituitary tumors.
Highlights
Humanin (HN) is a 24-amino acid peptide originally isolated from a cDNA library of surviving neurons of familial Alzheimer’s disease [1]
Our results indicate that HN exerted antiapoptotic action on anterior pituitary cells from female and male rats and that gonadal steroids regulated HNr expression, suggesting that HN could be involved in tissue homeostasis in this gland
To evaluate whether estrogens regulate the expression of HNr in the female pituitary, we assessed by fluorescence-activated cell sorter (FACS) HNr expression in anterior pituitary cells from SHAM-operated and OVX rats
Summary
Humanin (HN) is a 24-amino acid peptide originally isolated from a cDNA library of surviving neurons of familial Alzheimer’s disease [1]. The homologous rat gene encodes a 38 aminoacid peptide referred to as rattin (HNr). The origin of HN family peptides is controversial, hypotheses being that they may be encoded in either the mitochondrial or nuclear DNA [4,5,6]. HN has been detected in human skeletal muscle [9], plasma [10], testis and sperm [11]. HNr was shown to be expressed in a number of adult rat tissues such as cerebral cortex, hippocampus, heart, testis and uterus, among others [12]. HNr expression in the rat pituitary has not yet been explored
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