The anterior pituitary hormones can be classified according to hormone structure and the types of receptors that they activate. Growth hormone (GH) and prolactin (PRL), single-chain protein hormones with significant homology, form one group. Both hormones activate receptors of the JAK/STAT superfamily (see Chapter 2). Three pituitary hormones—thyroid-stimulating hormone (TSH, thyrotropin), follicle-stimulating hormone (FSH), and luteinizing hormone (LH)— are dimeric proteins that activate G protein-coupled receptors (see Chapter 2). TSH, FSH, and LH share a common α subunit. Their β subunits, though somewhat similar to each other, differ enough to confer receptor specificity. Finally, adrenocorticotropic hormone (ACTH), a peptide cleaved from a larger precursor, proopiomelanocortin (POMC) represents a third category. POMC can be cleaved into various other biologically active peptides like α-melanocyte-stimulating hormone (MSH) and β-endorphin
TABLE 37–1 Links between hypothalamic, anterior pituitary, and target organ hormone or mediator.1 1All of these hormones act through G protein-coupled receptors except GH and PRL, which act through JAK/STAT receptors.
2Endogenous GnRH, which is released in pulses, stimulates LH and FSH release. When administered continuously as a drug, GnRH and its analogs inhibit LH and FSH release through down-regulation of GnRH receptors. (+), stimulant; (−), inhibitor.
(see Chapter 31). Like TSH, LH, and FSH, ACTH acts through a G protein–coupled receptor. A unique feature of the ACTH receptor (also known as the melanocortin 2 receptor) is that a transmembrane protein, melanocortin 2 receptor accessory protein, is essential for normal ACTH receptor trafficking and signaling.
TSH, FSH, LH, and ACTH share similarities in the regulation of their release from the pituitary. Each is under the control of a distinctive hypothalamic peptide that stimulates their production by acting on G protein-coupled receptors (Table 37–1). TSH release is regulated by thyrotropin-releasing hormone (TRH), whereas the release of LH and FSH (known collectively as gonadotropins) is stimulated by pulses of gonadotropinreleasing hormone (GnRH). ACTH release is stimulated by corticotropin-releasing hormone (CRH). An important regulatory feature shared by these four structurally related hormones is that they and their hypothalamic releasing factors are subject to feedback inhibitory regulation by the hormones whose production they control. TSH and TRH production are inhibited by the two key thyroid hormones, thyroxine and triiodothyronine (see Chapter 38). Gonadotropin and GnRH production is inhibited in women by estrogen and progesterone, and in men by testosterone and other androgens. ACTH and CRH production are inhibited by cortisol. Feedback regulation is critical to the physiologic control of thyroid, adrenal cortical, and gonadal function and is also important in pharmacologic treatments that affect these systems.