ESPE Abstracts

The reproductive axis comprises the hypothalamus, the pituitary gland and the gonads. While all its components are assembled in the embryo, it only starts to be active postnatally, initially during a transient period known as minipuberty. Activity is re-initiated at puberty which marks the onset of reproductive capacity. The hypothalamic gonadotrophin releasing hormone (GnRH) has a central regulatory role because it controls production and secretion of the two gonadotrophins, luteinizing (LH) and follicle stimulating (FSH) hormones. These act in turn on the gonads, regulating steroid and gamete production. Gonadal steroids exert crucial feedback both at the hypothalamic and pituitary level. Gonadotrophs, secreting LH and FSH, initially arise in the embryonic pituitary. They are amongst the first endocrine cell types to commit, at 12.5dpc in the ventral pituitary primordium, with upregulation of the glycoprotein a, the subunit common to LH, FSH and TSH (thyroid stimulating hormone). LHb and FSHb subunits are only expressed at 16.5dpc in the mouse, which is considered the true gonadotroph birthdate. Postnatally, gonadotrophs invade the gland dorsally. We and others have shown that the pituitary comprises a population of stem cells (SCs) {Rizzoti, 2013 #472}{Andoniadou, 2013 #480}. While these do not appear to play a significant role during normal turn-over in the adult gland, we show here using a novel, efficient and more physiological doxycycline-dependant Sox2^rtTA lineage tracing tool that postnatal pituitary SCs mostly give rise to gonadotrophs during a period encompassing minipuberty, in both sexes. These gonadotrophs invade the gland at the exception of a small ventral domain, where embryonic gonadotrophs remain confined. The discovery of a dual origin for gonadotrophs may help understand aspects of gonadotrophin regulation and mechanisms of diseases affecting puberty.