On the other end, our results showed also that TLQP peptides in the pituitary and hypothalamus could be up-regulated by the oestradiol/progesterone. These hormones regulate also somatostatin, and being TLQP peptides present in such neurones, it is possible that steroid hormones could modulate both TLQP and somatostatin by the same mechanisms. Regarding the role of TLQP peptides in the median eminence, in view of their close relation to somatostatin seen also in pancreas and stomach, we tried to elucidate a possible bioactivity of TLQP-21 on somatostatin and on its GHRH neurone targets. We found that TLQP-21 up-regulated the GHRH production suggesting that such peptide could act promoting the growth at the hypothalamic level. When adult male mice were chronically treated with TLQP-21, physiological, molecular and behavioral parameters related to the GH axis were investigated, however, TLQP-21 did not modulate the GH axis. One could hypothesize that TLQP-21 may regulate GHRH through somatostatin neurones selectively at the median eminence level, instead when the same peptide is injected, only a little part could reach the median eminence. Further experiments are needed to ascertain the precise role of TLQP-21 on the growth mechanisms and the possible connections with the cycle. Regarding the other VGF peptides, also C-and N-terminus peptides changed in the hypothalamus, pituitary and plasma. However, for these peptides is more difficult to hypothesize mechanisms of action in view of the rare information regarding their involvement on reproduction. It could be only suggested that these peptides could have a neuroendocrine and/or endocrine activity on the estrous cycle, and their presence into kisspeptin neurones is intriguing because of the importance of this hormone in PI-103 reproductive mechanisms. Furthermore, also the presence of PGH peptides in gonadotrophs, GnRH neurones, plasma and especially within the oocyte, needs more investigation. In conclusion, various VGF peptides may regulate the hypothalamus-pituitary complex via specific neuroendocrine mechanisms. In particular, for TLQP peptides we may hypothesize different possible interacting ways of action on the reproduction including endocrine pathways largely involving the ovary as well as paracrine/autocrine mechanisms at both the pituitary and ovary levels. In addition, we also found evidence for an involvement of TLQP-21 on neuroendocrine mechanisms acting on promoting growth at the median eminence level. To achieve their native structure, secretory and membrane proteins exploit the vast array of chaperones and enzymes that reside in the endoplasmic reticulum, the port of entry into the secretory compartment. Here, they undergo stringent quality control : only properly folded and assembled proteins are given the green light and proceed along the secretory pathway. Proteins that fail to attain their native state are eventually retrotranslocated to the cytosol for proteasomal degradation. Not all proteins entering the ER are secreted or directed to the plasma membrane. Even if in some conditions the flux of cargo can become intense, resident proteins stop at the desired stations to maintain organelle identity and guarantee function.