Gonadotropin-releasing hormone (GnRH)-synthesizing neurons represent the final output pathway of the hypothalamus in the neuroendocrine control of reproduction. Pulsatile GnRH secretion into the hypophysial portal circulation regulates the synthesis and release of the two pituitary gonadotropins, LH and FSH, which in turn, govern gonadal functions. Gonadal sex steroid hormones exert positive and negative feedback effects on the neurosecretory output of GnRH neurons via mechanisms that are poorly understood. A major research focus of the Laboratory of Endocrine Neurobiology has been on the neuronal and hormonal mechanisms that regulate GnRH neuronal functions.
The sex hormone 17β-estradiol (E2) is primarily synthesized in maturing ovarian follicles. Cyclic changes in serum E2 levels across the menstrual cycle exert profound effects on reproductive tissues in women. E2 also plays an important role in the maintenance of normal limbic and cortical functions. Around menopause, when E2 levels decline the incidence of cognitive and mood disorders increases, which can be prevented with hormone replacement therapy. A major research interest of the Laboratory has been in the molecular mechanisms whereby E2 preserves good mood, capability of learning and processing memory via interactions with cortical and limbic structures. The classic actions of E2 are mediated by two estrogen receptor isoforms, ERα and ERβ. They are ligand-dependent transcription factors which regulate gene expression in the presence of E2. Prefrontal cortex (PFC) and the hippocampus are known targets of steroid hormone signaling.
With support of the European Framework Programmes (5-7), we have been collaborating with outstanding European research laboratories of this scientific field to elucidate novel neuronal and hormonal mechanisms that control metabolism centrally. These studies have explored several, new regulatory channels:
