Another important input to hypothalamic neurons and the pituitary gland is stress, either as systemic stress (e.g., hemorrhage, inflammation) or as processive stress (e.g., fear, anxiety). Major medical or surgical stress overrides the circadian clock and causes a pattern of persistent and exaggerated hormone release and metabolism that mobilizes endogenous fuels, such as glucose and free fatty acids, and augments their delivery to critical organs. Growth and reproductive processes, in contrast, are suppressed. In addition, cytokines released during inflammatory or immune responses, or both, directly regulate the release of hypothalamic releasing hormones and pituitary hormones.
Chemical Nature of Hormones
Hormones are classified biochemically as proteins/peptides, catecholamines, steroid hormones, or iodothyronines. The chemical nature of a hormone determines (1) how it is synthesized, stored, and released; (2) how it is transported in blood; (3) its biological half-life and mode of clearance; and (4) its cellular mechanism of action.
Protein and peptide hormones can be grouped into structurally related molecules that are encoded by gene families. Protein/peptide hormones obtain their specificity from their primary amino acid sequence and from posttranslational modifications, especially glycosylation.
Because protein/peptide hormones are destined for secretion outside the cell, their synthesis and processing are differently from those of proteins destined to remain within the cell or to be continuously added to the membrane (
Fig. 38.5 ). These hormones are synthesized on the polyribosome as larger preprohormones or prehormones. The nascent peptides have at their N-terminus a group of 15 to 30 amino acids called the signal peptide. The signal peptide interacts with a ribonucleoprotein particle, which ultimately directs the growing peptide chain through a pore •Fig. 38.4 Originofcircadianrhythmsinendocrineglandsecretion,metabolicprocesses,andbehavioralactivity.(ModifiedfromTurekFW.Recent Prog Horm Res. 1994;49:43.) a membrane-bound secretory vesicle that is subsequently released into the cytoplasm. The carbohydrate moiety of glycoproteins is added in the Golgi apparatus.
Most hormones are produced as prohormones. Prohormones harbor the peptide sequence of the active hormone within their primary sequence. However, prohormones are inactive or less active and require the action of endopeptidases to trim away the neighboring inactive sequences.
D Plasma ACTH Protein/peptide hormones are stored in the gland as membrane-bound secretory vesicles and are released by exocytosis through the regulated secretory pathway. Thus these hormones are not continually secreted. Rather, they are secreted in response to a stimulus through a mechanism of stimulus-secretion coupling. Regulated exocytosis requires energy, Ca++ , an intact cytoskeleton (microtubules, microfilaments), and the presence of coat proteins that specifically deliver secretory vesicles to the cell membrane.