Endocrine glands are ductless1. As stated in Lesson 1 of Chapter 1 (introduction to Endocrinology), unlike the other organ systems, such as cardiovascular, gastrointestinal, hepatobiliary, the nervous system, etc., the endocrine glands are not physically connected to each other. In this lesson, we will discuss these glands and their functions.
Endocrine glands1 secrete their products in the extracellular environment, not directly into the bloodstream as erroneously stated in books and other documents. Once in the extracellular milieu, these hormones can then be absorbed through the capillaries into the blood and exert their actions on distant or neighboring (paracrine signaling2) cells. As erroneously stated in certain books, videos, and other documents, these glands do not release hormones directly into the bloodstream. What are the endocrine glands?
- The pineal gland3,4 (1). The pineal gland is also referred to as the pineal body. It is a pinecone-shaped gland located posteriorly to the thalamus which secretes the hormone melatonin (Fig. 1), a derivative of tryptophan (Trp, W). It is a hydrophilic hormone that regulates the circadian rhythm. We will cover the pineal gland or melatonin in more detail in a separate chapter.
- The hypothalamus (2). The hypothalamus (figure 2) lies below the thalamus and above the pituitary gland. It regulates multiple functions depending on the anatomic nuclei. This endocrine gland contains three regions, which are the anterior, middle, and posterior regions5. The anterior region6-9 regulates body temperature, stress, circadian rhythm, reproductive cycle, sexual arousal, metabolism, water level/blood volume, and other processes we will discuss later in more detail. The middle region of the hypothalamus, also called tuberal region, has two main nuclei: the ventromedial and arcuate nuclei. These two nuclei are specialized in the control of appetite and growth and development. Finally, the posterior region of the hypothalamus is in charge of the regulation of body temperature. The hypothalamus secretes many hormones that control hormonal release from the pituitary, constituting the hypothalamus-pituitary axis. We will have multiple chapters dedicated to the HP axis.
- The pituitary gland (3). The pituitary10-16, often called the master gland, is a pea-sized gland located below the hypothalamus. It controls several other endocrine glands. It is housed in the part of the skull called pituitary or hypophyseal fossa or sella turcica, beneath the optic chiasma. This is significant for the potential compression of the optic nerve in cases of large pituitary tumors. The gland consists of anterior (adenohypophysis) and posterior parts with different hormonal functions. The hypothalamus is linked to the pituitary gland by a vascular structure called the stalk, functionally forming the HP axis, as previously stated. This HP axis partly allows the integration of the endocrine and the nervous systems. The pituitary gland affects multiple other organs including the thyroid, the musculoskeletal system, the reproductive system, lactation during pregnancy, labor and delivery, fluid balance, and more. Similar to the hypothalamus, the pituitary gland secretes multiple hormones. We will cover the HP axis in detail in several other chapters.
- Parathyroid (4). The parathyroid17-22 is a set of 2 small pairs of glands that lie anteriorly in the vicinity of the thyroid gland. The parathyroid controls blood levels of calcium through the release of the parathyroid hormone (PTH), also called parathormone or parathyrin. PTH causes bone resorption resulting in the release of calcium from bone, with a concomitant increase in serum calcium level.
- The thyroid (5). The thyroid17,23-27 is an endocrine gland that is located anteriorly to the larynx, and more specifically below the large cartilage called Adam’s apple. It is composed of 2 lobes
- that are intersected by the isthmus. The gland regulates metabolism through the secretion of thyroid hormones (T3 and T4, hydrophobic amine hormones) and calcitonin (polypeptide hormone). The latter opposes the action of PTH by causing calcium deposition in bones (inhibits osteoclasts and stimulates osteoblasts), decreased calcium serum level, and inhibits intestinal absorption of calcium (Calcium from your diet).Although TH is an amino acid derivative, it is a hydrophobic hormone. Unlike the steroid (cholesterol-derived), however, Th does not cross the plasma membrane of its target cells freely. The transfer of TH (T3 and T4) across the blood-brain barrier is mediated by the transporters monocarboxylate 8 (MCT8) and organic anion transporter protein 1 (OATP1). T4 is converted to the active hormone T3 by deiodinase 2 (D2). More detailed covered of TH to follow in another chapter.
- Thymus. The thymus gland28-35 is located in the chest right above the heart but midline to it. It controls the development of the T lymphocytes. The thymus is one example of how the endocrine system is integrated with the immune system. The thymus secretes thymosin and thymopoietin.
- Adrenal gland. The adrenal gland36-41 is located superiorly to the kidneys (suprarenal) and regulates fluid balance, metabolism, stress response, and more. The adrenal gland secretes glucocorticoids, androgens, adrenaline, and noradrenaline.
- The pancreas. The pancreas42-52 is located in the upper half of the abdomen behind the stomach. It is more than an endocrine gland. It plays a crucial role in digestion (exocrine function). Its endocrine role is to control blood sugar via the islets of Langerhans that synthesize and secrete important hormones that are absorbed into the bloodstream. These hormones are insulin, which lowers blood sugar, and glucagon, which raises blood glucose. The endocrine function of the pancreas will be discussed later.
- Testes. The testes (male gonads)53-59 are a pair of oval-shaped endocrine organs that regulate reproduction in males. They secrete estradiol, inhibin, and the male hormones testosterone and dihydrotestosterone. Testosterone is produced from cholesterol by Leydig cells in the testes. It is converted by 5α-reductase into a more potent form 5α-dihydrotestosterone (DIT). Testosterone and DHT are ligands for androgen receptors, which are harbored by many cell types such as skeletal muscle, brain, kidney, and others. The adrenal glands also produce androgens, which are weaker than testosterone and DHT. Of note, androgens may undergo peripheral aromatization resulting in the conversion of testosterone to estrogen. One example of this peripheral conversion is gynecomastia, male breast enlargement due to an imbalance between testosterone and estrogen levels.
- The female endocrine reproductive system (10) consists of the uterus, the placenta, and the ovaries (female gonads)60-75. These organs secrete hormones that produce the egg (ovum), support fertilization and pregnancy. The placenta is formed only during pregnancy and secretes the female hormones (estrogen and progesterone), inhibin, human chorionic gonadotropin, and human placental lactogen. The uterus secretes the hormones relaxin and prolactin only during pregnancy. Finally, the ovaries secrete the typical female hormones estrogen and progesterone, the androgen androstenedione, and inhibin.
While these are the classical endocrine glands, it is important to keep in mind that the endocrine system is much broader than the hormones secreted by the classical endocrine glands. The heart, the liver (IGF, THPO), the stomach (gastrin, ghrelin, somatostatin, histamine, neuropeptide Y), and the kidney all produce and secrete hormones that serve to maintain homeostasis. We will cover all of them in this course. Specific PowerPoint slides and videos will be added later for each lesson.