Gonadotrophin-releasing hormone and kisspeptin: It takes two to tango.

Kisspeptin (Kp), a family of peptides comprising products of the Kiss1 gene, was discovered 20 years ago; it is recognised as the major factor controlling the activity of the gonadotrophin-releasing hormone (GnRH) neurones and thus the activation of the reproductive axis in mammals. It has been widely documented that the effects of Kp on reproduction through its action on GnRH neurones are mediated by the GPR54 receptor. Kp controls the activation of the reproductive axis at puberty, maintains reproductive axis activity in adults and is involved in triggering ovulation in some species.

Beta-nerve growth factor stimulates spontaneous electrical activity of in vitro embryonic mouse GnRH neurons through a P75 mediated-mechanism.

The control of ovulation helps guarantee the success of reproduction and as such, contributes to the fitness of a species. In mammals, two types of ovulation are observed: induced and spontaneous ovulation. Recent work on camelids, that are induced ovulators, highlighted the role of a factor present in seminal plasma, beta Nerve Growth Factor (β-NGF), as the factor that triggers ovulation in a GnRH dependent manner.

Thrombospondin-1 (TSP-1), a new bone morphogenetic protein-2 and -4 (BMP-2/4) antagonist identified in pituitary cells.

Bone morphogenetic proteins (BMPs) regulate diverse cellular responses during embryogenesis and in adulthood including cell differentiation, proliferation, and death in various tissues. In the adult pituitary, BMPs participate in the control of hormone secretion and cell proliferation, suggesting a potential endocrine/paracrine role for BMPs, but some of the mechanisms are unclear. Here, using a bioactivity test based on embryonic cells (C3H10T1/2) transfected with a BMP-responsive element, we sought to determine whether pituitary cells secrete BMPs or BMP antagonists.

Cellular mechanisms and integrative timing of neuroendocrine control of GnRH secretion by kisspeptin.

The hypothalamus integrates endogenous and exogenous inputs to control the pituitary-gonadal axis. The ultimate hypothalamic influence on reproductive activity is mediated through timely secretion of GnRH in the portal blood, which modulates the release of gonadotropins from the pituitary. In this context neurons expressing the RF-amide neuropeptide kisspeptin present required features to fulfill the role of the long sought-after hypothalamic integrative centre governing the stimulation of GnRH neurons.

Transducing properties of a pre-structured α-helical DPT-peptide containing a short canine adenovirus type 2 E4orf4 PP2A1-binding sequence.

Background: Induction of the death pathway resulting from the specific interaction of the PP2A1 phosphatase with adenoviral E4orf4 protein is a promising approach for cancer therapy. With the aim of deregulating tumor pathways, and mimicking E4orf4 anti-cancer signal, we have previously proposed the DPT technology concept, based on design of specific PP1/PP2A interacting penetrating peptides.

Methods: Using biochemical, structural and cell survival experiments, we have characterized new DPT-peptides containing short PP2A binding sequences.