Adenohypophysis Cell Types: Hormonal Production and Action, Hypothalamic Regulation, and Feedback Regulation •Fig. 41.8 Theoriginalgenetranscriptofproopiomelanocortincontainsstructuresofmultiplebioactivecompounds.ACTH,adrenocorticotropichormone;CLIP,corticotropin-likeintermediatepeptide;MSH,melanocyte-stimulatinghormone.NotethatACTHistheonlybioactivepeptidereleasedbythehumancorticotrope.
•Fig. 41.9 NormallevelsofACTHactontheMC2Rtoincreasecortisol.SupraphysiologicallevelsofACTHduetodecreasedcortisolproductionactonboththeMC2RandtheMC1Ronmelanocytesandcauseskindarkening.(ModifiedfromPorterfieldSP,WhiteBA.Endocrine Physiology. 3rded.Philadelphia:Mosby;2007.)UV light Keratinocytes in skin Melanocytes in skin PKA Pituitary corticotrope POMC expression ACTH secretion ACTH (physiological levels) Cortisol Diverse physiological effects ACTH (supraphysiological levels) In particular ° Blood glucose ˛ Inflammatory response High affinity binding to MC2R Low affinity binding to MC1R • Loss of feedback in Addison’s disease Physiological, high affinity PKA Steroidogenesis Cell growth ˝-MSH ° POMC expression Skin darkening Release of CRH at median eminence CRH neurons Cortisol (−) Cortisol (−) CRH CRH-R1 Adrenal cortex PKA ° Melanin synthesis and dispersal (e.g., infection), stimulate ACTH. The stress effects are mediated through CRH and ADH via the CNS. The response to many forms of severe stress can persist despite negative feedback from high cortisol levels. This means the hypothalamus has the ability to alter the set point of the HPA axis in response to stress. Severe chronic depression can reset the HPA axis as a result of hypersecretion of CRH and is a factor in the development of tertiary hypercortisolism.
Cortisol exerts negative feedback on the pituitary, where it suppresses POMC gene expression and ACTH secretion, and on the hypothalamus, where it decreases pro-CRH gene expression and release of CRH. Because cortisol has profound effects on the immune system (see ), the HPA axis and the immune system are closely coupled. Moreover, cytokines—particularly interleukin (IL)-1, IL-2, and IL-6—stimulate the HPA axis.
Thyrotropes regulate thyroid function by secreting the hormone TSH (thyrotropin) as part of the hypothalamic-pituitary-thyroid axis. TSH is one of three pituitary glycoprotein hormones (see
Table 41.1) that also include
FSH and LH (discussed later). TSH is a heterodimer composed of an α subunit, called the α-glycoprotein subunit (α-GSU), and a β subunit (β-TSH) (
Fig. 41.12 ). The α-GSU is common to TSH, FSH, and LH, whereas the β subunit is hormone specific (i.e., β-TSH, β-FSH, and β-LH are all unique). Glycosylation of the subunits increases their stability in circulation and enhances the affinity and specificity of the hormones for their receptors. The half-lives of TSH, FSH, and LH (and an LH-like placental glycoprotein hormone, human chorionic gonadotropin [hCG]) are relatively long, ranging from tens of minutes to several hours.
TSH binds to the TSH receptor on thyroid follicle cells (see
Chapter 42). As discussed in