The hypothalamic hormonal control of GH and prolactin differs from the regulatory systems for TSH, FSH, LH, and ACTH. The hypothalamus secretes two hormones that regulate GH; growth hormone-releasing hormone (GHRH) stimulates GH production, whereas the peptide somatostatin (SST) inhibits GH production. GH and its primary peripheral mediator, insulin-like growth factor-I (IGF-I), also provide feedback to inhibit GH release. Prolactin production is inhibited by the catecholamine dopamine acting through the D2 subtype of dopamine receptors. The hypothalamus does not produce a hormone that specifically stimulates prolactin secretion, although TRH can stimulate prolactin release, particularly when TRH concentrations are high in the setting of primary hypothyroidism.
Whereas all the pituitary and hypothalamic hormones described previously are available for use in humans, only a few are of major clinical importance. Because of the greater ease of administration of target endocrine gland hormones or their synthetic analogs, the related hypothalamic and pituitary hormones are used infrequently as treatments. However, many of them (TRH, TSH, CRH, ACTH, GnRH, GHRH) are used for specialized diagnostic testing. These agents are described in Tables 37–2 and 37–3 and are not discussed further in this chapter. In contrast, GH, SST,
TABLE 37–2 Clinical uses of hypothalamic hormones and their analogs.
Growth hormone-Used rarely as a diagnostic test for GH and releasing hormone GHRH sufficiency (GHRH)
Thyrotropin-May be used to diagnose TRH or TSH releasinghormone deficiencies; not currently available for (TRH, protirelin) clinical use in United States
Corticotropin-releasing Used rarely to distinguish Cushing’s disease hormone (CRH) from ectopic ACTH secretion
Gonadotropin-May be used in a single dose to assess releasing hormone initiation of puberty (pubertal gonadotropin (GnRH) response)
May be used in pulses to treat infertility caused by GnRH deficiency
Analogs used in long-acting formulations to inhibit gonadal function in children with precocious puberty, in some transgender/ gender variant early pubertal adolescents (to block endogenous puberty), in men with prostate cancer and women undergoing assisted reproductive technology (ART) or women who require ovarian suppression for a gynecologic disorder
Dopamine Dopamine agonists (eg, bromocriptine, cabergoline) used for treatment of hyperprolactinemia
LH, FSH, GnRH, and dopamine or analogs of these hormones are commonly used and are described in the following text.
Growth hormone, an anterior pituitary hormone, is required during childhood and adolescence for attainment of normal adult size and has important effects throughout postnatal life on lipid and carbohydrate metabolism, and on lean body mass and bone density. Its growth-promoting effects are primarily mediated via IGF-I (also known as somatomedin C). Individuals with congenital or acquired deficiency of GH during childhood or adolescence fail to reach their midparental target adult height and have disproportionately increased body fat and decreased muscle mass. Adults with GH deficiency also have disproportionately low lean body mass.
A. Structure