THE ENDOCRINE SYSTEM AND CHEMICAL MESSENGERS

Introduction

Hormones are chemical messengers synthesized by special endocrine and other cells and transported by the blood to target cells where they affect cell function by altering specific biochemical processes. Specificity of response is ensured by the presence on or in target cells of protein receptors that bind only selected hormones. Hormone effects are vastly amplified in target cells by acting through one of two basic mechanisms. Many hormones including epinephrine, glucagon, vasopressin, and some hormones of the anterior pituitary, cause production of a “second messenger”: such as cyclic AMP, that relays the hormone’s message from a surface receptor to a cell’s biochemical machinery. Steroid hormones and thyroid hormones operate through nuclear receptors. A hormone-receptor complex is formed that alters protein synthesis by stimulating or inhibiting gene transcription. Most invertebrate hormones are products of neurosecretory cells. The best understood invertebrate endocrine system is that controlling molting and metamorphosis in insects. A juvenile insect grows by passing through a series of molts under control of two hormones, one (ecdysone) favoring molting to an adult and the other (juvenile hormone) favoring retention of juvenile characteristics. Ecdysone is under the control of a neurosecretory hormone (PTH) from the brain.

The vertebrate endocrine system is orchestrated by the hypothalamus. Release of all anterior pituitary hormones is primarily regulated by hypothalamic neurosecretory products called releasing hormones (or release-inhibiting hormones). The hypothalamus also produces two neurosecretory hormones, which are stored in and released from the posterior lobe of the pituitary. In mammals these two hormones are oxytocin, which stimulates milk production and uterine contractions during parturition: and vasopressin (antidiuretic hormone), which acts on the kidney to restrict urine production, causes vasoconstriction of blood vessels, and increases thirst. In amphibians, reptiles, and birds vasotocin replaces vasopressin as the water-balance hormone.

The anterior lobe of the pituitary produces seven well-characterized hormones. Four of these are tropic hormones that regulate subservient endocrine glands: thyrotropic (=thyrotrophic) hormone (TSH), which controls secretion of thyroid hormones: adrenocorticotropic hormone (ACTH), which stimulates release of steroid hormones by the adrenal cortex; and luteinizing hormone (LH), which act on ovaries and testes. Three direct-acting hormones are (1) prolactin, which plays, several diverse roles, including stimulation of milk production; (2) growth hormone, which governs body growth and metabolism; and (3) melanocyte stimulating hormone (MSH), which controls melanocyte dispersion in ectothermic vertebrates.

The pineal gland, a derivative of the pineal complex of the diencephalon of the brain, produces the hormone melatonin. In many vertebrates, melatonin, which is released in response to darkness, maintains circadian rhythms. In birds and mammals that are seasonal breeders, melatonin provides information regarding day length, and thereby indirectly regulates seasonal reproductive activity.

Recent application of ultra sensitive radio immunochemical techniques has revealed many neuropeptides in the brain, several of which behave as neurotransmitters in the brain but as hormones elsewhere in the body. The classical definition of a hormone has been modified to include other chemical messengers, such as prostaglandins and cytokines, which originate in sources other than clearly defined endocrine glands.

Several hormones play important roles in regulating cellular metabolic activities. Two thyroid hormones, triiodothyronine (13) and thyroxine (T4), control growth, development of the nervous system, and cellular metabolism. Calcium metabolism is regulated principally by three hormones; parathyroid hormone from the parathyroid glands, a hormonal derivative of vitamin D, 1, 25-dihydroxyvitamin D, and calcitonin from the thyroid gland. Parathyroid hormone and 1, 25-dihydroxyvitamin D increase plasma calcium levels; calcitonin decreases plasma calcium levels.

The principal steroid hormones of the adrenal cortex are glucocorticoids, which stimulate formation of glucose from nonglucose sources (gluconeogenesis), and mineralocorticoids, which regulate blood electrolyte balance. The adrenal medulla is the source of epinephrine and norepinephrine, which have many affects, including assisting the sympathetic nervous system in emergency responses. They also increase energy substrates in the blood for use in emergency situations.

Glucose metabolism is regulated by the antagonistic action of two pancreatic hormones. Insulin is needed for cellular use of blood glucose and uptake of amino acids in muscle. Glucagon opposes the action of insulin.

The most recently discovered hormone, leptin, is secreted by adipose tissue and feeds back to the hypothalamus to modulate food intake and energy balance.

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