The document discusses several key topics in endocrine physiology: 1. It describes early endocrine experiments in the 1800s by Berthold and Bernard that helped establish the concepts of hormone targets and homeostasis. 2. It summarizes the major classes of hormones - peptides/proteins, amines, steroids, and eicosanoids - and how they are synthesized and regulated. 3. Feedback control mechanisms, especially negative feedback loops, are a major way the endocrine system regulates hormone production and maintains homeostasis.

1. Endocrine Physiology Dale Buchanan Hales, PhD Department of Physiology & Biophysics

4. Claude Bernard (1813-1878) Claude Bernard stated that the endocrine system regulates the internal milieu of an animal. The “internal secretions” were liberated by one part of the body, traveled via the bloodstream to distant targets cells . Circa 1854 Bernard's charge was to demonstrate that medicine, in order to progress, must be founded on experimental physiology.

9. Sensing and signaling Endocrine “glands” synthesize and store hormones. These glands have a sensing and signaling system which regulate the duration and magnitude of hormone release via feedback from the target cell.

13. A cell is a target because is has a specific receptor for the hormone Most hormones circulate in blood, coming into contact with essentially all cells. However, a given hormone usually affects only a limited number of cells, which are called target cells . A target cell responds to a hormone because it bears receptors for the hormone.

15. Types of cell-to-cell signaling Classic endocrine hormones travel via bloodstream to target cells; neurohormones are released via synapses and travel via the bloostream; paracrine hormones act on adjacent cells and autocrine hormones are released and act on the cell that secreted them. Also, intracrine hormones act within the cell that produces them.

22. Peptide/protein hormone synthesis

25. Thyroid hormones

27. Synthesis of catecholamines

33. Steroids can be transformed to active steroid in target cell

34. Steroidogenic Enzymes Common name "Old" name Current name Side-chain cleavage enzyme; desmolase P450 SCC CYP11A1 3 beta-hydroxysteroid dehydrogenase 3 beta-HSD 3 beta-HSD 17 alpha-hydroxylase/17,20 lyase P450 C17 CYP17 21-hydroxylase P450 C21 CYP21A2 11 beta-hydroxylase P450 C11 CYP11B1 Aldosterone synthase P450 C11AS CYP11B2 Aromatase P450 aro CYP19

36. Steroid hormone synthesis All steroid hormones are derived from cholesterol. A series of enzymatic steps in the mitochondria and ER of steroidogenic tissues convert cholesterol into all of the other steroid hormones and intermediates. The rate-limiting step in this process is the transport of free cholesterol from the cytoplasm into mitochondria . This step is carried out by the Steroidogenic Acute Regulatory Protein (StAR)

38. cholesterol Extracellular lipoprotein Cholesterol pool LH ATP cAMP PKA+ Pregnenolone Progesterone Androstenedione TESTOSTERONE 3  HSD P450c17 17  HSD acetate

45. Control of Endocrine Activity Rate of production: Synthesis and secretion of hormones are the most highly regulated aspect of endocrine control. Such control is mediated by positive and negative feedback circuits, as described below in more detail.

48. Feedback Control of Hormone Production Feedback loops are used extensively to regulate secretion of hormones in the hypothalamic-pituitary axis. An important example of a negative feedback loop is seen in control of thyroid hormone secretion

49. Inputs to endocrine cells

54. Circadian (chronotropic) control

55. Circadian Clock

59. Negative feedback effects of cortisol

61. Feedback control of insulin by glucose concentrations