Molecular economy of nature with two thyrotropins from different parts of the pituitary: pars tuberalis thyroid-stimulating hormone and pars distalis thyroid-stimulating hormone.

Thyrotropin (TSH) is classically known to be regulated by negative feedback from thyroid hormones and stimulated by thyrotropin-releasing hormone (TRH) from the hypothalamus. At the end of the 1990s, studies showed that thyrotroph cells from the pars tuberalis (PT) did not have TRH receptors and their TSH regulation was independent from TRH stimulation. Instead, PT-thyrotroph cells were shown to have melatonin-1 (MT-1) receptors and melatonin secretion from the pineal gland stimulates TSH-β subunit formation in PT. Electron microscopy examinations also revealed some important differences between PT and pars distalis (PD) thyrotrophs. PT-TSH also have low bioactivity in the peripheral circulation. Studies showed that they have different glycosylations and PT-TSH forms macro-TSH complexes in the periphery and has a longer half-life. Photoperiodism affects LH levels in animals via decreased melatonin causing increased TSH-β subunit expression and induction of deiodinase-2 (DIO-2) in the brain. Mammals need a light stimulus carried into the suprachiasmatic nucleus (which is a circadian clock) and then transferred to the pineal gland to synthesize melatonin, but birds have deep brain receptors and they are stimulated directly by light stimuli to have increased PT-TSH, without the need for melatonin. Photoperiodic regulations via TSH and DIO 2/3 also have a role in appetite, seasonal immune regulation, food intake and nest-making behaviour in animals. Since humans have no clear seasonal breeding period, such studies as recent ''domestication locus'' studies in poultry are interesting. PT-TSH that works like a neurotransmitter in the brain may become an important target for future studies about humans.