Endocrine system, introduction to endocrinology lesson 1: Hi, I am developing (update is continuous) this course on Luloot Academy for those interested in basic concepts in Endocrinology. I am a physician scientist, and you can check out my background here on my professional website. This Endocrinology course will consist of text with images initially. Then I will add PowerPoint slides and videos over time. As new materials are added, previous chapters will be modified for linking to other chapters and concepts. In addition, these chapters may be updated continuously based on new research findings or for more clarity. The first topic for this course is some basic concepts to introduce you to the field of Endocrinology, which is the study of the endocrine organs and the hormones that they secrete. Briefly, it is the study of the endocrine system. So the big question is what is the endocrine system?
Endocrine system Key concepts: hormones, paracrine, endocrine, autocrine, hormone receptor, ligand
Definition of the Endocrine system
If you think of the organ systems—the cardiovascular, gastrointestinal, musculoskeletal, respiratory, reproductive, and the nervous systems—they are made of physically connected components. The components of the neuroendocrine system1, on the other hands, are not anatomically linked to each other. Based on this observation, we can define the endocrine system as a cohesive complex of organs which release hormones targeting either neighboring cells or distant tissues.
So how do we define hormones? Hormones are chemical messengers that regulate homeostasis (constant internal environment) by exerting their action on either neighboring or distant target tissues. I have to caution you that you will read on the internet or even in books (or watch on educational videos) that hormones are chemical messengers secreted directly into the bloodstream. That statement is factually incorrect! Why is it an inaccurate statement about hormones? Think about it for a moment. All cells release their secretions in the extracellular milieu, which could directly lead to a duct, the extracellular matrix, or the circulatory system. The latter can only occur if those secretory cells are already inside the systemic circulation or in direct contact with the blood (e.g., erythrocytes, leukocytes). Does that make sense? The endocrine organs or tissues are not directly in contact with the blood. Therefore, they could not, in any way, release their hormones directly into the bloodstream. In fact, depending on the target cells, hormones can be classified as paracrine, autocrine, and endocrine hormones. The definition of hormones as chemicals targeting distant tissues is an outdated (old, classical) definition2. In fact, the endocrine system is integrated with other regulatory systems such as the nervous system (neuroendocrine) and the immune system (neuroendocrine-immune)1,3,4. Together, all these integrated components make up the endocrine system. Hormones do not just come from endocrine glands. They may also come from other organs such as the heart (atrial natriuretic peptide5), the liver (insulin-like growth factor 1)6, and adipose tissue (leptin)7. This brings up the following question.
What are the different types of hormones of the endocrine system in the context of the cells that their target?
There are many ways to classify hormones such as solubility, structure, target cells, etc. Today we will focus on hormonal classification based on target cell signaling. There are four types of endocrine system hormones: autocrine, paracrine, neurocrine, and endocrine (classical) hormones. Autocrine hormones are agents that exert their action on the cells from which they are secreted. It also means that those (autocrine) secretory cells carry the receptor specific to that hormone. It does not mean that the autocrine agents cannot have a distant target, as they can be both autocrine and endocrine. This is why it is most accurate to refer to autocrine, paracrine, neurocrine, and endocrine as signaling processes based on the location of the target cell (Figure 1). Paracrine hormones, as you may have already guessed, exert their actions on neighboring cells after they are secreted. Again, those hormones can also be absorbed into the bloodstream and reach these target cells through the systemic circulation as well. Paracrine and autocrine agents (unless they are also endocrine) are not consistent with the classical (old) definition of the hormones of the endocrine system. Similar to paracrine, Neurocrine hormones are released from nerve cells to reach adjacent target cells. Finally, endocrine hormones are those chemicals that are secreted in the extracellular milieu and then absorbed into the bloodstream via the capillaries. Once in the blood, the hormones are transported throughout the body and will only exert their action when they reach their target cells, which carry the receptors that are specific to these hormones. These are the classical hormones of the endocrine system.
A question you may ask is why all of these chemicals are part of the endocrine system and studied under endocrinology. Well, it is because hormones, when they were first discovered, were thought to be capable of targeting only distant tissues or cells. To better understand this, you can think of the systemic circulation as a superhighway. The hormone would be a person inside a vehicle. If you are a hormone going to a specific address, you may exit the highway prematurely or pass your exit. Once you get out through the wrong exit, you will never go to another address and knock on the wrong door. Instead, you would re-enter the highway until you go through the correct exit and reach the correct address. It is the same thing for a hormone. The correct address is the target that carries the hormone receptor. That is, a cell which carries a receptor that only a particular hormone can recognize
Important concepts of the endocrine system:
Endocrine (classical) signaling (e.g., Thyroid hormone)8 is initiated by chemical messengers (hormones) secreted on one part of the body and transported through the systemic circulation to another part of the body to arouse the activity of a target cell.
Paracrine signaling (e.g., Somatostatin)9 is regulated by chemical messengers (hormones) that arouse the activity of a neighboring cell. Some paracrine agents may also have endocrine or autocrine function.
Autocrine signaling (e.g., histamine)10-19 is initiated by hormones that arouse the activity of the cells (autocrine cells) that secrete them.
Intracrine hormones (e.g., progesterone) 20-25 are chemicals that exert intracellular action on the cells that secrete them.
This hormonal classification of the endocrine system is, therefore, based on the signaling processes related to the location of the target cells.
In conclusion, the endocrine system is an integrated network of organs that release hormones targeting neighboring or distant cells to maintain homeostasis
Stay tuned for updates and next lesson: Glands and hormonal classification (types of hormones)
References for the advanced reader
- Pittman QJ. A neuro-endocrine-immune symphony. J Neuroendocrinol. 2011;23(12):1296-1297.
- Pelosio C. [Definition of hormones]. Policlinico Prat. 1954;61(40):1332-1333.
- Sakane T, Suzuki N. Neuro-endocrine-immune axis in human rheumatoid arthritis. Arch Immunol Ther Exp (Warsz). 2000;48(5):417-427.
- Huang Y, Lu SJ, Dong JX, Li F. The new proof of neuro-endocrine-immune network-expression of islet amyloid polypeptide in plasma cells in gastric mucosa of peptic ulcer patients. World J Gastroenterol. 2000;6(3):417-418.
- Ogawa H, Qiu Y, Huang L, Tam-Chang SW, Young HS, Misono KS. Structure of the atrial natriuretic peptide receptor extracellular domain in the unbound and hormone-bound states by single-particle electron microscopy. FEBS J. 2009;276(5):1347-1355.
- Nambam B, Schatz D. Growth hormone and insulin-like growth factor-I axis in type 1 diabetes. Growth Horm IGF Res. 2018;38:49-52.
- Odle AK, Akhter N, Syed MM, et al. Leptin Regulation of Gonadotrope Gonadotropin-Releasing Hormone Receptors As a Metabolic Checkpoint and Gateway to Reproductive Competence. Front Endocrinol (Lausanne). 2017;8:367.
- Brufsky AM, Dickler MN. Estrogen Receptor-Positive Breast Cancer: Exploiting Signaling Pathways Implicated in Endocrine Resistance. Oncologist. 2018.
- Malaisse WJ. Paracrine control of glucagon release by somatostatin (Review). Int J Mol Med. 2014;33(3):491-498.
- Tang J, Liao Y, He S, et al. Autocrine parathyroid hormone-like hormone promotes intrahepatic cholangiocarcinoma cell proliferation via increased ERK/JNK-ATF2-cyclinD1 signaling. J Transl Med. 2017;15(1):238.
- Baskari S, Govatati S, Madhuri V, et al. Influence of autocrine growth hormone on NF-kappaB activation leading to epithelial-mesenchymal transition of mammary carcinoma. Tumour Biol. 2017;39(10):1010428317719121.
- Ansari N, Ho PW, Crimeen-Irwin B, et al. Autocrine and Paracrine Regulation of the Murine Skeleton by Osteocyte-Derived Parathyroid Hormone-Related Protein. J Bone Miner Res. 2018;33(1):137-153.
- Chen YJ, You ML, Chong QY, et al. Autocrine Human Growth Hormone Promotes Invasive and Cancer Stem Cell-Like Behavior of Hepatocellular Carcinoma Cells by STAT3 Dependent Inhibition of CLAUDIN-1 Expression. Int J Mol Sci. 2017;18(6).
- Lents CA, Thorson JF, Desaulniers AT, White BR. RFamide-related peptide 3 and gonadotropin-releasing hormone-II are autocrine-paracrine regulators of testicular function in the boar. Mol Reprod Dev. 2017;84(9):994-1003.
- Falus A, Hegyesi H, Lazar-Molnar E, Pos Z, Laszlo V, Darvas Z. Paracrine and autocrine interactions in melanoma: histamine is a relevant player in local regulation. Trends Immunol. 2001;22(12):648-652.
- Molnar EL, Cricco G, Martin G, et al. Histamine as a potential autocrine regulator of melanoma. Inflamm Res. 2001;50 Suppl 2:S102-103.
- Rivera ES, Cricco GP, Engel NI, Fitzsimons CP, Martin GA, Bergoc RM. Histamine as an autocrine growth factor: an unusual role for a widespread mediator. Semin Cancer Biol. 2000;10(1):15-23.
- Malaviya R, Uckun FM. Histamine as an autocrine regulator of leukemic cell proliferation. Leuk Lymphoma. 2000;36(3-4):367-373.
- Cricco GP, Davio CA, Martin G, et al. Histamine as an autocrine growth factor in experimental mammary carcinomas. Agents Actions. 1994;43(1-2):17-20.
- Re RN. Cardiac angiotensin II: an intracrine hormone? Am J Hypertens. 2003;16(5 Pt 1):426-427.
- Re RN. Toward a theory of intracrine hormone action. Regul Pept. 2002;106(1-3):1-6.
- Re RN. The origins of intracrine hormone action. Am J Med Sci. 2002;323(1):43-48.
- Gujral A, Burton DW, Terkeltaub R, Deftos LJ. Parathyroid hormone-related protein induces interleukin 8 production by prostate cancer cells via a novel intracrine mechanism not mediated by its classical nuclear localization sequence. Cancer Res. 2001;61(5):2282-2288.
- Re R. The nature of intracrine peptide hormone action. Hypertension. 1999;34(4 Pt 1):534-538.
- Conkright MD, Asem EK. Intracrine role of progesterone in follicle-stimulating hormone- and cyclic adenosine 3′,5′-monophosphate-induced fibronectin production and deposition by chicken granulosa cells: influence of follicular development. Endocrinology. 1995;136(6):2641-2651.