Abstract
The hypothalamus-pituitary axis consists of two brain structures, the hypothalamus and the pituitary gland, connected by the pituitary stalk. This axis has a major physiological role since it allows the release of hormones in the body and regulates processes such as growth, development, reproduction and body homeostasis.The pituitary gland consists of two distinct major parts: the adenohypophysis and the neurohypophysis. The former possesses networks of endocrine cells that allow the release of hormones under the control of hypothalamic parvocellular neurons, while the latter directly receives neuronal terminals from hypothalamic magnocellular neurons, allowing the secretion of two neurohormones: oxytocin and vasopressin. The secreted oxytocin will play a role during parturition, in the production and ejection of milk or during a hypertonic osmotic shock. Regarding vasopressin, its two major roles are water reabsorption in kidney collecting ducts and vasoconstriction during dehydration.Bloodstream is directly linked to the hypothalamic-pituitary axis and plays a major role in the capture and distribution of hormones in the body. Indeed, there are two plexuses of dense networks of fenestrated capillaries at the level of the external face of the median eminence and the adenohypophyseal parenchyma connected by the vessels of the pituitary stalk. In addition, at the level of the neurohypophysis, there is a plexus of fenestrated capillaries which, together with hypothalamic neuronal endings, form neurohemal junctions, thus allowing the capture of neurohormones to release them into the systemic circulation.My thesis consisted in exploring the link between a neuroendocrine system and the fenestrated vascular system within the neurohypophysis in mouse models. I studied whether the secretion of a neurohypophyseal hormone, vasopressin, leads to changes in the neurohypophyseal microcirculation. To do so, I focused on three features of this neuro-hemal junction. Firstly, I studied the basal activity of the vasopressin terminals both in vivo and ex vivo, and whether vasopressin has a local effect on these terminals. Secondly, I investigated whether stimulation of vasopressin neurons by dehydration has the capability to modulate neurohypophyseal capillary blood flow and whether pericytes - contractile mural cells - are involved in this blood flow regulation. Thirdly, I developed a fluorescent vasopressin-sensitive biosensor to monitor vasopressin levels in real time.My results unveiled that the activity of vasopressin terminals in the neurohypophysis was modulated by vasopressin itself, due to a positive feedback control mediated by both vasopressin V1a and oxytocin receptors. During dehydration, although there was no difference in the overall velocity of neurohypophyseal fenestrated capillaries, there were differences within individual capillaries. Some vessels displayed decreases in red blood cell (RBC) velocities while others showed RBC velocity increases, thus leading to a stable average flow within the capillary network in the neurohypophysis. These changes in RBC velocities were most likely mediated by pericytes since upon stimulation with vasopressin, cytosolic calcium increased in pericytes, indicating their contraction and possibly vasoconstriction of the capillaries. Our developed biosensor allowed real-time detection of vasopressin in vitro, thus within a range of neurohormone concentrations compatible with the values estimated in vivo in the neurohypophysis.