Ca++ and PKC TSH synthesis TSH secretion TSH PKA • All aspects of thyroid  hormone synthesis and secretion • Cell growth CNS inputs Diurnal rhythm T3 (−) T4, T 3 T3 (−) TRH TRH receptor TSH receptor Pituitary thyrotrope Thyroid epithelial cell •Fig. 41.13 Hypothalamic-pituitary-thyroidaxis.PKA,proteinkinaseA;PKC,proteinkinaseC;T3,triiodothyronine(activeformofthyroidhormone);T4,thyroxine;TRH,thyrotropin-releasinghormone;TSH,thyroid-stimulatinghormone.(ModifiedfromPorterfieldSP,WhiteBA.Endocrine Physiology. 3rded.Philadelphia:Mosby;2007.) hypothalamic neurons, is a tripeptide with cyclization of a glutamine at its N-terminus (pyro-Glu) and an amidated C-terminus. TRH is synthesized as a larger prohormone that contains six copies of TRH within its sequence. It binds to the TRH receptor on thyrotropes (Fig. 41.13 ). TRH neurons are regulated by numerous CNS-mediated stimuli, and TRH is released according to a diurnal rhythm (highest during overnight hours, lowest around dinner time). TRH secretion is also regulated by stress, but in contrast to CRH, stress inhibits secretion of TRH. This includes physical stress, starvation, and infection. Triiodothyronine (T3) and thyroxine (T4) (the latter via type 2 deiodinase-mediated conversion to T3; see ) negatively feed back on both pituitary thyrotropes and TRH-producing neurons. Thyroid hormone represses both β-TSH expression and the sensitivity of pituitary thyrotropes to TRH while also inhibiting TRH production and secretion by parvocellular neurons.
Duringembryonicdevelopment,GnRHneuronsmigratetothemediobasalhypothalamusfromthenasalplacode.PatientswithKallmann syndrome havetertiary hypogonadotropic hypogonadism, oftenassociatedwithlossofthesenseofsmell(anosmia).ThisisduetoamutationintheKAL gene, whichresultsinfailureoftheGnRHneuronalprecursorstoproperlymigratetothehypothalamusandestablishaneurovascularlinktotheparsdistalis.
The Gonadotrope
The gonadotrope secretes FSH and LH (collectively called gonadotropins) and regulates the function of gonads in both sexes. As such the gonadotrope plays an integral role in the hypothalamic-pituitary-testis axis and the hypothalamic-pituitary-ovarian axis (
Fig. 41.14
FSH and LH are segregated into different secretory granules and are not co-secreted in equimolar amounts (in contrast to ADH and neurophysin, for example). This allows independent regulation and secretion of FSH/LH by gonadotropes. The actions of FSH and LH on gonadal function are complex, especially in women, and will be discussed in detail in . In general, gonadotropins promote testosterone secretion in men and estrogen and progesterone secretion in women. FSH also increases secretion of a transforming growth factor (TGF)-β–related protein hormone called inhibin in both sexes.
FSH and LH secretion are regulated by one hypothalamic releasing hormone, gonadotropin-releasing hormone (GnRH; formerly called LHRH). GnRH is a 10–amino acid peptide produced by a subset of parvocellular hypothalamic GnRH neurons (see