A novel model of action for TSH in the mammalian neuroendocrine system

In mammals, day-length-sensitive (photoperiodic) seasonal breeding cycles depend on the pineal hormone melatonin, which modulates secretion of reproductive hormones by the anterior pituitary gland. It is thought that melatonin acts in the hypothalamus to control reproduction through the release of neurosecretory signals into the pituitary portal blood supply, where they act on pituitary endocrine cells. Contrastingly, the work presented here shows that during the reproductive response of Soay sheep exposed to summer day lengths, the reverse applies. Melatonin acts directly on anterior-pituitary cells, and these then relay the photoperiodic message back into the hypothalamus to control neuroendocrine output. The switch to long days causes melatonin-responsive cells in the pars tuberalis (PT) of the anterior pituitary to increase production of thyrotrophin (TSH). This acts locally on TSH receptor (TSH-R)-expressing cells in the adjacent mediobasal hypothalamus, leading to increased expression of type II thyroid hormone deiodinase (DIO2). DIO2 initiates the summer response by increasing hypothalamic triiodothyronine (T3) levels. The present work also reports similar expression of TSH-R, TSH and DIO2 in European hamster, while DIO3 was oppositely regulated. These data and recent findings in quail indicate that the TSH-expressing cells of the PT play an ancestral role in seasonal reproductive control in vertebrates. In mammals this provides the missing link between the pineal melatonin signal and thyroid-dependent seasonal biology.EThOS - Electronic Theses Online ServiceGBUnited Kingdo