Ernest Starling, a few years after he coined the word 'hormone'. Picture with permission from the Starling family.

Conservation of endocrine glands in two evolutionarily distant vertebrates, which produce similar hormones but whose actions may vary according to the species and target tissue (Gorbman & Bern, 1962).

Two examples of how information received in the central nervous system is converted to chemical signals by endocrine cascades leading to important physiological regulatory functions. The upward and downward arrows indicate negative (−ve) and positive (+ve) feedback loops, respectively. TSH-releasing hormone (TRH) and corticotrophic-releasing factor (CRF) are produced by the hypothalamus and act on the pituitary to produce thyroid-stimulating hormone (TSH) and adrenocorticotrophic hormone (ACTH), which regulate the activities of the thyroid and adrenal glands, respectively. GC, glucocorticoids; TH, thyroid hormone.

A simplified diagram to illustrate 'second messenger' and protein phosphorylation pathways associated with target-cell membrane receptors for three hormones: epinephrine (adrenaline), insulin and prolactin. AC, adenylyl cyclase; cAMP, cyclic AMP; DG, diacylglycerol; Gs and Gi, stimulatory and inhibitory G proteins; IP₃, inositide trisphosphate; IRS, insulin receptor substrate; JAK, Janus kinase; PI, phosphatidyl inositol; PK-A and PK-C, phosphokinases A and C; PL-C, phospholipase C; PY, phosphotyrosine; Rα/Rβ, IR and PRLR, receptors for epinephrine, insulin and prolactin, respectively; STAT, signal transduction and transcription factor. The grey squares indicate different protein targets for phosphorylation by different pathways, depending on hormonal signal, species and tissue.

Nuclear hormone receptors form complexes with other factors to regulate transcription. A bridging protein such as CBP/p300 would be in close contact with nuclear receptors and transcription factors (Tf) that recognize specific DNA sequences—TATA box binding protein (TBP) and transcription factor IIB (TFIIB), which would form a complex with RNA polymerase II (PolII). CBP/p300 is thought to form complexes with other transcription factors without involving DNA, such as CREB, AP1 and Sap1a. The activities of many of these components are modified by phosphorylation.

Convergence of signalling through membrane and nuclear receptors. Latent intracellular regulatory factors can be activated (or inhibited) directly by phosphorylation (green), proteolysis (pink) or second messenger fluctuations (blue), as indicated by arrows of different colours. The activities of nuclear proteins, receptors and transcription factors can thus be modified by phosphorylation through plasma membrane receptors (Brivanlou & Darnell, 2002).