Hormones in mammals

Mammals are vertebrate animals that have fur (hair) and that nourish their young with milk by means of mammary glands, which are modified sweat glands. Mammals include, among other animals, primates (such as humans and chimpanzees), cetaceans (such as whales and dolphins), and marsupials (such as kangaroos, koalas, and opossums). Mammals are sexually reproducing and diploid (having two copies of every chromosome). During fertilization, a sperm from the male parent unites with an egg from the female parent to produce a diploid single-celled zygote. The zygote contains all the genetic information for all the cells of the future individual. The zygote divides first into two cells, then four, eight, sixteen, thirty-two, and so on.

As the cells divide, they begin to specialize, so that different groups of cells assume unique functions. Some cells become nerve cells, others skin cells, and others blood cells. A number of factors, including hormones, contribute to differentiation.

Throughout the development of the organism, profound changes such as birth, puberty, menopause, aging, and death occur. Progressive changes in cell functions contribute to these sequential processes. Many of these developmental changes are controlled by hormones, chemical messengers that provide communication between cells located in different portions of the body via the bloodstream.

The Endocrine System

Hormones fall into the two principal categories of protein hormones and steroid hormones. Protein hormones are composed of protein—long chains of amino acids encoded by genes. Steroid hormones are derivatives of cholesterol. Both hormone types function in the same fashion: They control genes. Hormones are produced and secreted from a source endocrine gland and are then transported through the bloodstream to a target tissue, where they penetrate cells and concentrate on the control regions of genes located on chromosomes. Once at a control region, a given hormone either activates or inactivates the gene. If a gene is activated, messenger RNA will be produced, leading to protein production. If a hormone inactivates a gene, protein production will cease. A given hormone may activate certain genes and inactivate others.

Endocrine glands are ductless glands (glands that lack channels for secreting their products) that produce and secrete hormones into the bloodstream. Major mammalian endocrine glands include the hypothalamus, hypophysis, thyroid, parathyroids, thymus, pancreas, adrenals, and gonads. The hormones secreted from these glands influence many cells and each other during mammalian development.

Homeostasis, the maintenance of a constant internal environment, is a major objective of endocrine hormones. They work antagonistically (against each other) to maintain various body conditions (such as blood sugar and calcium levels) in equilibrium. Endocrine hormones work principally, but not exclusively, by negative feedback. For example, a region of the brain called the hypothalamus reacts to various body conditions by releasing hormones that stimulate the nearby hypophysis (the pituitary gland) to release certain of its hormones. The hypophyseal hormones direct other glands and tissues to respond in a particular fashion. Once bodily conditions are back to normal, the hypothalamus terminates its initial stimulatory hormones, thereby stopping the entire sequence of events.

The hypothalamus controls a number of critical body functions, including the activities of endocrine glands, body temperature, wake and sleep cycles, and appetite. Ultimately, all these functions involve some type of hormones. When various conditions occur in the body (for example, hyperthermia, which is increased body heat), genes in certain hypothalamic cells synthesize special proteins called releasing factors that are sent into the bloodstream to activate target cells in glands (in the example cited, sweat glands) located elsewhere in the body. Often, the target of hypothalamic releasing factors is a nearby endocrine gland called the hypophysis, also known as the pituitary, or “master gland.”

Regulating the Reproductive Cycle

The eight hormones known to be released from the hypophysis gland are vasopressin (the “antidiuretic hormone”), oxytocin, prolactin, growth hormone, thyrotropin, adrenocorticotropic hormone (ACTH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). Vasopressin is released in response to low water levels in the blood; it stimulates the kidneys to retain water, reduce urine output, and increase blood pressure until blood water levels return to normal, upon which it will no longer be produced. Oxytocin causes muscular contractions in the uterus during childbirth and in the breast for the secretion of milk for an infant. Prolactin is present in males and females, but it is functional only in females. It stimulates milk production from fat deposits in the breast. Growth hormone causes growth in children. It is present in adults but contributes only to the control of metabolic rate. Thyrotropin stimulates the thyroid gland to produce and secrete various hormones that control metabolism (examples: thyroxine and triiodothyronine). Adrenocorticotropic hormone stimulates the adrenal cortex, located above each kidney, to release its metabolism-controlling steroid hormones. At puberty, follicle-stimulating hormone stimulates the female ovarian follicle to mature and begin producing the steroid hormone estrogen; it directs the male testes to begin producing sperm. Also, at puberty, luteinizing hormone stimulates the ovary to begin producing eggs and the steroid hormone progesterone, which directs the testes to begin producing the steroid hormone testosterone.

The hypophyseal hormones, all proteins encoded by genes, have a major impact upon metabolism and development in mammals. This is especially true for the sexual cycle hypophyseal hormones FSH and LH. In females, puberty begins with the first menstrual cycle. Each menstrual cycle is the female body’s way of preparing for a possible pregnancy. At the beginning of the cycle, the hypophysis produces high concentrations of FSH, which stimulates the ovarian follicle to develop and produce estrogen, a steroid hormone that increases body fat in regions such as the buttocks and breasts. Simultaneously, increased LH production matures the egg in the ovarian follicle and stimulates progesterone production. Progesterone causes the endometrium (the lining of the uterus) to increase its blood vessel content and thickness for receiving and maintaining a fertilized egg and for the subsequent long gestation period (nine months in humans). If the egg is fertilized by sperm, it will adhere to the endometrium, and progesterone will continue to be secreted to maintain the endometrium and the pregnancy. If the egg is not fertilized, progesterone levels will drop, estrogen levels will rise, the endometrium will be sloughed away (menstrual bleeding will occur), and the cycle will start all over again.

The primate female menstrual cycle is only one very complex example of how hormones are intricately involved in mammalian developmental processes. There are many subtler aspects of the menstrual cycle that still are not well understood, such as the identity of the hormonal signal from the fertilized egg that stimulates the female ovary to continue progesterone production for continuation of the pregnancy. All mammalian hormones are interconnected by cause-and-effect relationships. Tremendous research remains before a clear and complete picture of hormonally controlled mammalian development will emerge.

Regulating Other Functions

The thyroid gland, located in the throat region, produces several hormones (examples: thyroxine and triiodothyronine) that elevate the body’s metabolic rate. The thyroid also secretes a hormone called calcitonin, which works antagonistically with the hormone parathormone produced by the adjacent parathyroid glands. When blood calcium is high (as in a condition called hypercalcemia), the calcitonin gene in thyroid cells begins producing the protein hormone calcitonin, which stimulates bone cells called osteoblasts to build more bone, thereby removing calcium from the bloodstream. Once blood calcium levels are back to normal, calcitonin production halts. In hypercalcemia, the parathormone gene in parathyroid cells begins producing parathormone (also a protein hormone) that stimulates bone cells called osteoclasts to break down bone, thereby restoring blood calcium levels but possibly contributing to osteoporosis (bones that are brittle because of calcium deficiency) and other bone-related disorders. Parathormone production is stopped once blood calcium levels are back to normal.

The islets of Langerhans in the pancreas secrete two antagonistic protein hormones—insulin and glucagon. In response to high glucose levels in the blood (as in hyperglycemia), genes in beta cells produce and secrete insulin, which directs body cells, especially liver cells, to absorb glucose and store it as a polysaccharide called glycogen. Insulin production will stop once blood glucose levels are reduced to normal. An insulin deficiency leads to prolonged hyperglycemia, a serious and often fatal disorder called diabetes mellitus. When blood glucose levels are too low (as in hypoglycemia), genes in the alpha cells of the islets of Langerhans produce and secrete glucagon, which directs body cells to break down their glycogen reserves and begin releasing glucose back into the bloodstream until normal blood glucose levels are reached, upon which glucagon production ceases.

Further endocrine glands include the adrenal cortex, located on top of each kidney, which secretes three major classes of steroid hormones: the glucocorticoids such as cortisol, which controls fat and protein metabolism; the mineralocorticoids such as aldosterone, which controls blood sodium levels; and the androgens (male sex steroids). The adrenal medulla, located internally to the adrenal cortex, is derived from nervous tissue and secretes two hormones, epinephrine and norepinephrine, that double as excitatory neurotransmitters at nerve axon endings; chemical energy transmission between nerve cells occurs at synapses, or gaps, between adjacent neurons. Neurotransmitters are protein hormones that relay electrical impulses from one neuron (nerve cell) to another throughout the trillion-cell nervous systems of mammals. Other neurotransmitters include the excitatory acetylcholine and inhibitors glycine, enkephalin, and gamma-aminobutyric acid.

The kidney secretes the protein hormone erythropoietin when the blood has a low red blood cell level; erythropoietin stimulates the undifferentiated stem cells called hemocytoblasts in the red bone marrow of flat bones (ribs, sternum) to differentiate and develop into mature red blood cells. Platelet-derived growth factor (PDGF) is released from damaged blood vessels to activate platelet cells to begin blood clotting. Macrophage colony stimulatory factor and eosinophil chemotactic factor are two hormones that both activate and attract certain respective immune system cells to the site of an infection or allergic reaction. Histamine is released from damaged tissue and causes blood vessel dilation, so that the vessels are more leaky, thus allowing hormones and other molecules to reach the injury site, eventually leading to the inflammation and itching associated with wound healing.

The hormone prostaglandin helps inflammation and contracts some smooth muscles located throughout the body; nerve growth factor stimulates the growth of sensory nerves throughout the body; and epidermal growth factor stimulates the growth of the epidermis, the outermost skin layer that is constantly being shed and replaced. Sunlight exposure to skin produces cholecalciferol, or vitamin D, which helps to stimulate bone growth and maintenance.

Developing the Full Hormonal Picture

The tally of mammalian hormones extends well beyond the molecules just discussed. What is most puzzling is how hormones are interconnected during the control of development. Hormones control gene activities of target cells, and some simple hormone systems act antagonistically (calcitonin-parathormone, insulin-glucagon). Yet there has not emerged a clear and complete picture of the overall interactions. Hormones control an incredibly complex array of cellular activities from conception to death.

Mammalian developmental hormones have been studied using a variety of biochemical and physiological experiments: isolation and purification experiments, injection into experimental animals, studies of metabolic disorders in animals, and molecular genetics experiments. Protein structures based upon genetic and biochemical studies are well understood. Steroid hormone structures have been unraveled from studies of cholesterol biochemistry.

Dissections of experimental animals yield intact endocrine glands (such as the thyroid and pancreas) that can be used to show function. Chemical secretions from these glands can be extracted and separated into the various hormone components by several biochemical techniques such as electrophoresis, chromatography, and centrifugation. The isolated hormones can be further purified by rerunning them through these separatory techniques.

Electrophoresis involves the separation of molecules in an electric field based upon their sizes and charges. Large molecules move slowly, whereas small, compact molecules move more quickly. Protein hormones move from the negative pole to the positive pole in electrophoretic gels. Affinity chromatography involves placing membrane hormone receptor proteins on a vertical column containing a porous resin. The specific hormone type that binds to this particular target receptor protein will stick to the resin. Nonbinding hormones will wash through the column. Finally, ultracentrifugation separates molecules based upon size in incredibly high-spinning gravity fields measuring about 100,000 times the earth’s gravity. These three techniques, plus a few others, are very effective in isolating and purifying hormones as well as other important molecules.

Isolated hormones have been injected into experimental organisms and organ extracts, followed by observation and recording of the animal’s physiological responses. For example, injection of vasopressin reduces an animal’s urine output while simultaneously producing a slight blood pressure rise. Injection of insulin lowers blood sugar levels, which is why diabetics are prescribed insulin. Such experiments require the use of experimental animals, and extracts from these animals, which has sparked considerable controversy and debate concerning animal rights. These studies are important in understanding the physiology of the human body.

Genetic studies, such as cloning and DNA sequencing, have identified genes that may encode other developmental hormones. Discovery of the homeobox within the genes of all mammals indicates that there are some proteins (hormones) that control basic pattern development in mammals during early embryonic development. Some researchers believe that there may be certain hormones that accelerate aging and cause death in later life.

Hormones as a Key to Understanding Genes

All mammals start as a single-celled zygote—an egg that has been fertilized by sperm—that undergoes a rapid sequence of mitotic divisions until it reaches the stage of a hollow, microscopic ball of identical cells called the blastula. Signaling molecules called hormones stimulate the blastula to fold in upon itself and form layers of tissue that gradually become differentiated into organs because of the presence of other hormones, which affect the tissue in sequence. Still other hormones later influence the interactions of organ systems for the smooth function of the organism. Knowledge of the chemical mechanisms and sequences through which hormones exert their effects will provide the key to understanding the action of genes, which in a more fundamental way, are responsible for the various stages of life. Hormones direct cellular differentiation and development in the organism for the rest of its life. Hormones will be crucially involved in fetal development, birth, early growth and development, puberty, reproductive cycles, aging, and eventually death. Hormones control virtually all aspects of an organism’s life.

If certain relevant mammalian developmental hormones can be identified, then target cells—cells that respond to the hormones in discrete but interrelated ways—may also be determined. A “developmental profile” for any organism would then be a real possibility, and the control of any organism’s development, even behavior, could result, although this may pose ethical problems.

Currently, there is some detailed knowledge of the functions of many developmental hormones. Many hormones remain to be identified, however, and the overall scheme of hormonal control of development is still sketchy. Extensive research will be needed in the future.

Principal Terms

Endocrine System: An array of ductless glands scattered throughout the mammalian body that produce and secrete hormones directly into the bloodstream

Homeobox: A set of genes that encode proteins involved in development of a wide range of animal species, from nematodes to insects to mammals

Homeostasis: The maintenance of constant conditions within the internal environment of an organism, a process controlled by antagonistic hormone pairs

Hypophysis: The pituitary gland, or “master” gland, which produces and secretes at least eight protein hormones influencing growth, metabolism, and sexual development

Hypothalamus: A brain region just below the cerebrum that interconnects the nervous and endocrine systems of mammals, thereby controlling most hormone production and many body functions

Neurotransmitter: A signaling molecule that provides neuron-to-neuron communication in animal nervous systems; some double as hormones

Protein Hormone: A hormone type composed of protein, a long chain of amino acids encoded by a gene

Steroid Hormone: A hormone type derived from cholesterol, a type of fat molecule

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