The synthesis and secretion of thyroid-stimulating hormone (TSH) and the various factors involved in thyroid hormone production are illustrated in Figure 41.13. Calcium ions (Ca++) and protein kinase C (PKC) play a role in TSH synthesis and secretion. TSH is produced by pituitary thyrotrope cells and acts on thyroid epithelial cells. Triiodothyronine (T3) and thyroxine (T4) negatively regulate TSH and thyrotropin-releasing hormone (TRH) production through feedback inhibition. TRH, a tripeptide synthesized by hypothalamic neurons, binds to TRH receptors on thyrotropes. The secretion of TRH is regulated by various central nervous system (CNS) stimuli and follows a diurnal rhythm. Stress inhibits TRH secretion. 

During embryonic development, gonadotropin-releasing hormone (GnRH) neurons migrate to the mediobasal hypothalamus from the nasal placode. Kallmann syndrome, characterized by tertiary hypogonadotropic hypogonadism and anosmia (loss of smell), is caused by a mutation in the KAL gene, which impairs the migration of GnRH neuronal precursors to the hypothalamus. This disrupts the establishment of a neurovascular link to the pars distalis.

The gonadotrope, responsible for the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), plays a crucial role in the hypothalamic-pituitary-testis axis and the hypothalamic-pituitary-ovarian axis (Figure 41.14). FSH and LH are stored separately in secretory granules and are not co-secreted in equal amounts. This allows for independent regulation and secretion of FSH and LH. The effects of FSH and LH on gonadal function are complex, particularly in women, and will be discussed further. These gonadotropins stimulate testosterone secretion in men and estrogen and progesterone secretion in women. Additionally, FSH increases the secretion of inhibin, a transforming growth factor (TGF)-β–related protein hormone, in both sexes.

The secretion of FSH and LH is regulated by gonadotropin-releasing hormone (GnRH), previously known as LHRH. GnRH is a 10-amino acid peptide produced by a subset of parvocellular hypothalamic GnRH neurons. (Source: Porterfield SP, White BA. Endocrine Physiology. 3rd ed. Philadelphia: Mosby; 2007.)
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