3 The Endocrine System

Endocrine signaling and homeostasis

The endocrine system is a network of glands and hormone-secreting cells that coordinates body functions and helps maintain homeostasis. Hormones travel through the blood to target cells and change their activity. Compared with many nervous-system signals, endocrine signals can act over long distances, often develop more slowly, and may last longer. The nervous and endocrine systems also work together: nerve signals can prompt the adrenal glands to release hormones during stress.

Hormone-secreting cells occur in organs whose main roles are not endocrine, so hormonal regulation is distributed throughout the body rather than confined to a short list of glands.

Hormone types and target cells

A hormone is a chemical messenger released by cells into the bloodstream or nearby fluid. It affects only cells with the appropriate receptor, so the same hormone can circulate throughout the body while acting on particular tissues. A target cell’s response also depends on how many receptors it has and on its internal signaling machinery.

Hormones are grouped by chemical structure:

• Peptide and protein hormones, including insulin and growth hormone, are generally water-soluble and bind to receptors on the cell surface.

• Steroid hormones, including cortisol, estrogen, progesterone, and testosterone, are lipid-soluble and usually bind to receptors inside cells.

• Amine hormones are derived from amino acids. Epinephrine and norepinephrine bind to cell-surface receptors, while thyroid hormones act mainly through intracellular receptors.

How hormones change cell activity

Water-soluble hormones can bind to membrane receptors and activate intracellular relay molecules called second messengers. For example, a receptor may activate a G protein, leading to production of cyclic AMP (cAMP). cAMP activates proteins inside the cell, creating a signaling cascade that changes cell activity. Other pathways use calcium ions or inositol trisphosphate as messengers.

Lipid-soluble hormones can pass through the cell membrane and bind to receptors in the cytoplasm or nucleus. The resulting hormone–receptor complex can influence gene activity and change which proteins a cell makes. These responses often take longer to begin than rapid membrane-signaling effects, but may last longer.

Hormones can interact in different ways. They can have synergistic effects, working together; permissive effects, in which one hormone enables a full response to another; or antagonistic effects, in which they produce opposing responses. Insulin and glucagon have opposing effects on blood glucose.

Major endocrine organs and their hormones

The hypothalamus links nervous and endocrine control and regulates the pituitary through releasing and inhibiting hormones. It also makes oxytocin and antidiuretic hormone (ADH), which are stored and released by the posterior pituitary. The pituitary produces growth hormone (GH), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin. Together, pituitary hormones regulate growth, other endocrine glands, reproduction, and milk production.

The thyroid produces thyroxine (T₄) and triiodothyronine (T₃), which influence metabolic activity, growth, and development, as well as calcitonin, which can help lower blood calcium. The parathyroid glands produce parathyroid hormone (PTH), which raises blood calcium and helps regulate calcium balance.

The adrenal glands produce cortisol, aldosterone, epinephrine, and norepinephrine. These hormones support stress responses, metabolism, blood pressure, and salt-and-water balance. The adrenal medulla releases epinephrine and norepinephrine in response to sympathetic nerve signals.

The pancreatic islets produce insulin and glucagon, which help regulate blood glucose. The ovaries produce estrogens and progesterone, which support reproductive function, reproductive cycles, and pregnancy. The testes produce testosterone, which supports sperm production and male reproductive development and function. The pineal gland produces melatonin, which helps regulate daily sleep–wake rhythms.

Feedback and control of hormone release

Most hormone secretion is controlled by negative feedback: a change triggers a response that reduces the original change. This helps keep internal conditions within a functional range. In a typical endocrine axis, the hypothalamus signals the pituitary, the pituitary stimulates another gland, and the resulting hormone feeds back to reduce hypothalamic and pituitary signaling.

The thyroid axis illustrates this pattern. The hypothalamus releases thyrotropin-releasing hormone (TRH), which stimulates the pituitary to release TSH. TSH stimulates the thyroid to produce T₃ and T₄. As thyroid hormone levels rise, they inhibit further TRH and TSH release, limiting additional thyroid stimulation.

Hormone release can be triggered by different kinds of stimuli:

• Humoral stimuli: A change in a blood-borne substance triggers release. For example, rising blood glucose stimulates pancreatic cells to release insulin.

• Hormonal stimuli: One hormone prompts another gland to release a hormone; TSH stimulating the thyroid is an example.

• Neural stimuli: Nerve activity triggers secretion; sympathetic signals stimulate the adrenal medulla to release epinephrine and norepinephrine.

Positive feedback amplifies a response rather than reversing it. During childbirth, oxytocin strengthens uterine contractions, and contractions promote further oxytocin release. The loop ends when birth removes the stimulus.

Growth, metabolism, and blood glucose

Growth hormone, released by the anterior pituitary, supports tissue building and influences how the body uses nutrients. Some of its growth effects occur indirectly through insulin-like growth factors, including signals produced by the liver. Thyroid hormones are also essential to normal growth and development and regulate cellular metabolic activity.

Metabolism comprises the chemical processes by which cells use and store energy. Thyroid hormones help regulate overall metabolic activity, and cortisol affects how the body uses stored energy. Insulin and glucagon act in opposition to stabilize blood glucose.

After a meal, increased blood glucose stimulates pancreatic beta cells to release insulin. Insulin promotes glucose uptake by many cells and encourages glucose storage, including as glycogen in the liver and muscles. Between meals, falling blood glucose stimulates pancreatic alpha cells to release glucagon. Glucagon prompts the liver to release glucose, helping raise blood glucose toward its usual range.

Hormonal control of reproduction

Reproductive hormone regulation involves the hypothalamus, pituitary, and gonads. The hypothalamus releases gonadotropin-releasing hormone (GnRH), which stimulates the anterior pituitary to release FSH and LH. These hormones act on the ovaries or testes, supporting egg or sperm development and the production of sex hormones. Sex hormones generally feed back to the hypothalamus and pituitary to adjust further signaling.

One important exception to the usual inhibitory feedback pattern occurs shortly before ovulation: rising estrogen contributes to a surge in LH that triggers ovulation.