Hormones: Secretion and Action

1. Introduction

In human and other animals traffic of signals from one part of body to another part is sent via biomolecules synthesized and/or secreted by cells (or organs). The signalling may involve cell itself (autocrine signaling) or to a nearby target (paracrine signaling) or to the cell in contact/extracellular matrix (juxtacrine signaling) or to distintly located target (endocrine and exocrine signalling). Although, all of these are very important for regulation of bodily functions we will be discussing endocrine secretions and their role in regulation of different functions.

2. Hormones

  1. Hormones are non-nutritious signaling molecules that traffic information from one cell to another.
  2. Hormones are secreted by the endocrine organs directly in the extracellular fluid (ECF)/blood. Hormones travel through the soluble medium like the ECF.
  3. Hormones fall into one of a number of different hormonal classes (e.g., steroids, monoamines, peptides, proteins, eicosanoids).
  4. Hormones signal through a variety of general (e.g., nuclear vs cell surface) and specific (e.g., tyrosine kinase vs phosphoinositide turnover) mechanisms in target cells.
  5. Hormones produced in one tissue may promote or inhibit activity in a target cell/tissue.
  6. Hormones identify its target by the presence of receptors on the cells of the target tissue.
  7. Hormonal response occurs in minutes to hours.

3. Chemical Classes of Hormones

Hormones vary widely in chemical composition. They can be-

  • Proteins (eg. adrenocorticotrophin)
  • Glycosylated Proteins (eg. thyroid-stimulating hormone)
  • Dimerized Proteins (eg. follicle-stimulating hormone)
  • Peptide (eg. vasopressin)
  •  Monoamines (eg. norepinephrine)
  • Amino acid derivatives (eg. triiodothyronine, tetraiodothyronine)
  • Steroids (eg. cortisol)
  • Lipids (eg. prostaglandins)

4. Organs And Their Hormonal Secretions

4.1 Hypothalamus and Pituitary gland

The hypothalamus and pituitary gland function as a unit and exert control over function of several endocrine organs like thyroid, adrenals, and gonads as well as a wide range of physiologic activities. This unit is highly conserved across vertebrate species.

  • The Hypothalamus and Pituitary gland are anatomically related.
  • The Pituitary gland is divided in to two anatomical parts, the adenohypophysis and the neurohypophysis (pars nervosa).
  • Adenohypophysis consist of two portions, pars distalis and pars intermedia. The pars distalis is commonly called anterior pituitary. In humans, the pars intermedia is almost merged with pars distalis.
  • The pituitary gland lies at the base of the skull in a portion of the sphenoid bone called the Sella turcica (Turkish saddle). Hypothalamus lies just above the pituitary gland and below the thalamus; under surface of the brain. Schematic representation of hypothalamus and pituitary gland is shown below.

4.2 Hypothalamic Hormones and Function

The hypothalamic hormones include growth hormone releasing hormone(GRHR), somatostatin, dopamine, prolactin-releasing factors (PRF), thyrotropin releasing hormone (TRH), corticotropin releasing hormone (CRH), gonadotropin-releasing hormone (GnRH), oxytocin (OT) and anti diuretic hormone (ADH or vasopressin). The hypothalamic hormones are released via hypophysial portal blood vessels and the neurohypophysis (posterior pituitary).

4.2.1 Growth Hormone Releasing Hormone, GHRH

  • GHRH-secreting neurons are located in the arcuate nuclei of hypothalamus.
  • GHRH stimulates GH secretion.
  • The half-life of GHRH is approximately 3 to 7 minutes.

4.2.2 Somatostatin

  • Somatostatin is secreted by the cells located in the periventricular region of hypothalamus (and also from δ cells of pancreas).
  • Somatostatin inhibits GHRH secretion and thereby inhibit secretion of GH.
  • Somatostatin also inhibit secretion of TSH.
  • Somatostatin has a half-life of 2 to 3 minutes.

4.2.3 Dopamine

  • Dopamine-secreting neurons (tuberoinfundibular dopaminergic system) are located in the arcuate nuclei of the hypothalamus.
  • Dopamine inhibit PRL hormone by binding to the dopamine receptors.
  • It has a half-life of 1 to 2 minutes.

4.2.4 Thyrotropin-releasing hormone, TRH

  • TRH is secreted from paraventricular nuclei of the hypothalamus.
  • TRH is a tripeptide.
  • It regulates TSH secretion.
  • The half-life of TRH is approximately 6 minutes.

4.2.5 Prolactin-releasing factors, PRFs

  • PRL increase associated with sleep, during stress, and after nipple stimulation or suckling.
  • There is little evidence for its physiologic role.

4.2.6 Corticotropin-releasing hormone, CRH

  • CRH is secreted from paraventricular nuclei of hypothalamus.
  • CRH is also secreted from human placenta, therefore CRH level increases significantly during late pregnancy and delivery.
  • CRH mediate secretion of adrenocorticotropic hormone (ACTH).
  • The half-life of CRH is approximately 6 to 10 minutes and 40 to 50 minutes.

4.2.7 Gonadotropin-releasing hormone, GnRH

  • GnRH secreted by neurons located in the preoptic area of the anterior hypothalamus.
  • The secretion of LH and FSH is controlled by GnRH.
  • Low-frequency pulses of GnRH favor FSH release while high-frequency pulses favour LH release.
  • It has a half-life of 2 to 4 minutes.

4.2.8 Oxytocin, OT

  • Oxytocin is released from supraoptic nucleus of hypothalamus.
  • OT acts on smooth muscles and stimulate their contraction.
  • It regulates uterine contractions (during pregnancy & child birth) and milk ejection.
  • Oxytocin inhibits CRH-mediated ACTH secretion.

4.2.9 Anti diuretic hormone, ADH or Vasopressin

  • Vasopressin acts on smooth muscle cells around blood vessels to cause muscle contraction, which results in constriction of blood vessels and an increase in blood pressure.
  • Vasopressin also acts within the kidney to decrease water excretion in the urine, thus retaining fluid in the body and helping to maintain blood volume.

4.3 Anterior Pituitary Hormones and Function

The hormones secreted from posterior pituitary is synthesized in the different nuclei of hypothalamus. Posterior pituitary do not synthesize any hormone on their own. So, all the above discussed hormones (from 4.2.1 to 4.2.9) can be remembered as the hypothalamic synthesized hormones released from posterior pituitary. The next discussed hormones ACTH, GH, PRL, TSH, LH, and FSH are synthesized and secreted by the anterior pituitary gland.

4.3.1 Adrenocorticotropic hormone, ACTH

  • ACTH is synthesized in the corticotroph of anterior pituitary.
  • ACTH stimulates the secretion of glucocorticoids, mineralocorticoids, and androgens (all steroids from the adrenal cortex). ACTH is the inducer of steroidogenesis (through a cAMP dependent mechanism).
  • The ACTH secretion is mediated by CRH.
  • ACTH secretion increases in response to feeding in both humans and other animals.
  • Stress stimulates ACTH secretion.
  • Its half-life is 7-12 minutes.

4.3.2 Growth hormone, GH

  • GH also known as somatotropin.
  • It is synthesized and secreted by the somatotrophs of anterior pituitary.
  • The GH promote growth.
  • It promotes growth via insulin like growth factor-I (IGF-I).
  • GH secretion is inhibited by somatostatin.
  • Hypoglycemia (low blood sugar) stimulates GH release.
  • GH has a half-life of 10 to 20 minutes.

4.3.3 Prolactin, PRL

  • PRL is synthesized and secreted from the lactotrophs of the anterior pituitary.
  • PRL stimulates lactation in the postpartum (after child birth) period.
  • During pregnancy, PRL secretion increases and, in concert with many other hormones (estrogen, progesterone, hPL, insulin, and cortisol), promotes additional breast development in preparation for milk production (no role in the development of normal breast tissue in humans).
  • In men, excess PRL leads to decreased testosterone synthesis and decreased spermatogenesis.
  • PRL also has a role in immunomodulation. It modulates and stimulates both immune cell proliferation and survival.
  • Dopamine (secreted from hypothalamus) inhibit PRL secretion.
  • Half-life of PRL is 25 to 50 minutes.

4.3.4 Thyroid stimulating hormone, TSH

  • It is a glycoprotein.
  • TSH stimulates iodine uptake by thyroid; hormonogenesis, and release of T4 and T3.
  • TSH secretion also causes an increase in gland size and vascularity (blood supply).
  • TSH secretion is controlled by both stimulatory (TRH) and inhibitory (somatostatin) influences from the hypothalamus.
  • Half-life of TSH is 35 to 50 minutes.

4.3.5 Luteinizing hormone, LH and Follicular stimulating hormone, FSH

  • LH and FSH are glycoproteins secreted from the same cells of anterior pituitary.
  • LH and FSH bind to receptors in the ovary and testis and regulate gonadal function by promoting sex steroid production and gametogenesis.
  • Normal LH & FSH level vary with age of the person.
  • They are low before puberty and elevated in postmenopausal women.
  • A nightly rise of LH in boys and the cyclic secretion of FSH and LH in girls usually mark the onset of puberty before clinical signs are apparent.

In men:-

  • LH stimulates testosterone production from the interstitial cells of the testes (Leydig cells).
  • LH and FSH together causes maturation of spermatozoa.
  • FSH stimulates testicular growth.
  • FSH enhances the production of an androgen-binding protein (ABP) by the Sertoli cells, which are a component of the testicular tubule necessary for sustaining the maturing sperm cell.
  • LH and FSH levels in men are similar to those in women during the follicular phase (discussed in next section).

In women:-

  • LH stimulates estrogen and progesterone production from the ovary.
  • A surge (sudden increase) of LH in the mid-menstrual cycle is responsible for ovulation.
  • Continued LH secretion subsequently after ovulation stimulates the corpus luteum to produce progesterone by enhancing the conversion of cholesterol to pregnenolone.
  • Development of the ovarian follicle is largely under FSH control.
  • Secretion of estrogen from this ovarian follicle is dependent on both FSH and LH.
  • In women, LH and FSH vary during the menstrual cycle; during the initial phase of the cycle (follicular phase), LH steadily increases, with a midcycle surge that initiates ovulation (ovulation occurs approximately 10 to 12 hours after the LH peak and 24 to 36 hours after the estradiol peak). FSH, on the other hand, initially rises and then decreases during the later follicular phase until the midcycle surge, which is in agreement with LH. Both LH and FSH levels fall steadily after ovulation.

4.4 The Pineal Gland

The pineal gland is located at the roof of the posterior portion of third ventricle (diencephalon of the brain) .The pineal gland releases hormone melatonin. It is released during darkness but not during the daylight.

4.4.1 Melatonin

  • Melatonin is synthesized from serotonin.
  • Melatonin probably plays an important role in the setting of the body’s circadian rhythms.
  • The exact functions of melatonin in humans are uncertain.
  • Melatonin also influences pigmentation, metabolism, immune system and menstrual cycle.

4.5 The Thyroid Gland

The thyroid gland is a bilobed structure that sits within the neck straddling the trachea. Within the thyroid gland are numerous follicles, composed of an enclosed sphere of highly specialized cells surrounding a protein-rich core. These cells participate in almost all phases of thyroid hormone synthesis and secretion. The hormones synthesized and secreted by the thyroid gland are triiodothyronine (T3) and tetraiodothyronine (T4). The amount of T4 synthesized and secreted is more than that of T3. Iodine is required for normal level synthesis of thyroid hormones. A decrease in the level of thyroid hormones is called hypothyroidism (due to decreased iodine level) and increase in it is called hyperthyroidism. Additionally, thyroid also synthesize calcitonin.

4.5.1 Triiodothyronine, T3 and Tetraiodothyronine T4

  • Thyroid hormone stimulates carbohydrate absorption from the small intestine and increases fatty acid release from adipocytes. These actions provide energy to maintain the metabolic rate at a high level.
  • Thyroid hormones are needed for the normal production of growth hormones. Therefore, in the absence of TH, growth in children is decreased.
  • During fetal life, TH exerts many effects on central nervous development, including the formation of nerve terminals, production of synapses, growth of dendrites and dendritic extensions “spines”, and the formation of myelin.
  • The half-life of T4 (in plasma) is 7 days and that of T3 is 1 day.
  • Hypothalamic thyrotropin-releasing hormone (TRH) stimulates thyrotrophic cells in the anterior pituitary to produce TSH, which in turn promotes thyroid hormone (T3 and T4) secretion.

4.5.2 Calcitonin

The thyroid contains parafollicular or C cells that produce calcitonin, which inhibits bone resorption, but has no apparent physiologic role in humans.

4.6 Parathyroid Gland

Two pairs of parathyroid glands usually lie behind the upper and middle portions of the thyroid lobes. It produces parathyroid hormone (PTH).

4.6.1 Parathyroid hormone, PTH

  • Parathyroid hormone production is controlled by the extracellular calcium concentration.
  • Decreased calcium concentration stimulates PTH secretion, and an increased plasma calcium concentration inhibits PTH secretion.
  • PTH increases blood calcium ion level.
  • It increases the resorption of bone by osteoclasts, which results in the movement of calcium and phosphate from bone into extracellular fluid.
  • It increases renal tubular calcium re-absorption, thus decreasing urinary calcium excretion.
  • It reduces the tubular re-absorption of phosphate, thus raising its urinary excretion.
  • It stimulates the formation of 1, 25-dihydroxyvitamin D (also known as calcitriol, an active form of vitamin D) which then increases intestinal absorption of calcium and phosphate.

4.7 Thymus Gland

Thymus is a primary lymphoid organ (other one is bone marrow). The thymus lies in the upper part of the chest. Its size varies with age, being relatively large at birth and continuing to grow until puberty, then it gradually atrophies and is replaced by fatty tissue (in old age people). Thymus consists mainly of mature lymphocytes that will eventually migrate (via the blood) to the secondary lymphoid organs.

4.7.1 Thymopoietin

  • It releases a group of hormones collectively called thymopoietin.
  • The thymopoietin exerts regulatory role on T-lymphocyte maturation and function. Thus, it provides cell mediated immunity.
  • It promotes antibodies production and thus promote humoral immunity.

4.8 Adrenal Gland

A pair of adrenal gland is located at the anterior part of each kidney. The adrenal gland is divided into two parts. The outer part is cortex and the inner part is medulla. The adrenal cortex is further divided into three zones; Zona glomerulosa (outer side), Zona fasciculata and Zona reticularis (inner side). The adrenal cortex secrete hormones aldosterone, cortisol, corticosterone, dehydroepiandrosterone (DHEA), and androstenedione. The adrenal medulla secrete epinephrine (adrenaline) and nor-epinephrine (nor-adrenaline). Epinephrine and norepinephrine are together called catecholamines or “fight and flight hormones.”

4.8.1 Aldosterone

  • Aldosterone is known as a mineralocorticoid.
  • Its effects are on salt (mineral) balance, mainly on the kidneys’ handling of Sodium, Potassium and Hydrogen ions.

4.8.2 Cortisol and Corticosterone

  • Cortisol and corticosterone are called glucocorticoids.
  • These are involved in metabolism of glucose and other organic nutrients.
  • Cortisol exerts effect on the facilitation of stress responses.
  • Cortisol produces anti-inflammatory reactions suppressing the immune response. Thus, it regulates the immune system.
  • Cortisol stimulate RBC production.

4.8.3 Dehydroepiandrosterone, DHEA and androstenedione

  • DHEA and androstenedione belongs to the class of hormone called androgen (which also include testosterone from the testis).
  • They have functions similar to the testosterone.
  • Adrenal androgens are much less potent than testosterone, they are of little physiological significance in the adult male.
  • However, they play role in females and in foetal development.

4.8.4 Epinephrine and Nor-epinephrine

  • Epinephrine causes a large release of fatty acids from adipose tissue (in presence of thyroid hormone).
  • These are responsible in part for maintaining normal cardiac function.
  • Catecholamines stimulate glycolysis, lipolysis and proteolysis.
  • Catecholamines causes pupillary dilation, piloerection (raising of hairs), increases alertness and sweating.
  • They also increases heart beat, strength of heart contraction and rate of respiration.

4.9 Pancreas

Pancreas is functionally two organs the exocrine part and the endocrine part. The exocrine part releases digestive enzymes. The endocrine part consist of “Islet of Langerhans” having different types of cells which releases insulin, glucagon, somatostatin (also released from hypothalamus; see 4.2.2), pancreatic polypeptide (PP), and ghrelin hormones.

4.9.1 Insulin

  • Insulin is synthesized and secreted by pancreatic β cells.
  • Insulin is synthesized as preproinsulin which is then processed into proinsulin followed by another round of processing to form insulin.
  • Insulin consists of 51 amino acids contained within two peptide chains: an A chain, (with 21 amino acids) and a B chain (with 30 amino acids). The chains are connected by two disulfide bonds.
  • The main function of insulin is to promote storage of ingested nutrients.
  • Insulin Promotes glucose storage as glycogen.
  • It inhibits glycogenolysis (removal of glucose from glycogen).
  • It decreases appetite and increases energy expenditure.
  • Insulin causes decreases in blood glucose level, hence called hypoglycemic hormone.
  • Insulin has half-life of 3 to 5 minutes.

4.9.2 Glucagon

  • Glucagon is synthesized and secreted by pancreatic α cells.
  • Glucagon is synthesized as proglucagon which is then processed into glucagon. It is a single chain polypeptide of 29 amino acids.
  •  glucagon provides a mechanism for delivering energy from the liver to the other tissues between meals.
  • It reverses the process of insulin i.e. it promotes glycogenolysis (more glucose is flushed into the blood) and other sugar synthesizing process.
  • Glucagon causes increase in blood glucose level, hence called hyperglycemic hormone.
  • It has half-life of 3 to 6 minutes.

4.9.3 Pancreatic Polypeptide, PP and Ghrelin

  • Pancreatic Polypeptide (PP) is derived from PP cells of pancreas.
  • The mature PP is 36 amino acid polypeptide.
  • Although it is involved in the regulation of exocrine pancreatic secretion and gall bladder contraction, the physiologic actions of PP remain uncertain.
  • The pancreatic cells (and P/D1 endocrine cells in the gastric mucosa, and a few cells in the heart, lung, kidney, immune system, hypothalamus, and pituitary) secrete ghrelin.
  • Ghrelin is 28 amino acid peptide.
  • Ghrelin stimulates growth hormone secretion.
  • Ghrelin induces gastric emptying and acid secretion.
  • Ghrelin also regulates appetite and energy balance.

4.10 Testis and Ovary

Testis is primary male sex organ present in scrotum outside the abdomen. It is composed of many types of cells and tube structures which includes Leydig (interstitial) cells and seminiferous tubules. The main androgen hormone secreted from testes is testosterone.
In females, the primary sex organ is a pair of ovaries located within the abdomen. it is not only store for germ cells but also produces hormones required for reproduction and development of secondary sexual characteristics. The main hormones secreted are estrogens and progesterone.

4.10.1 Testosterone and other androgens

  • It causes proper development of primary sex characteristics in males. Deficiency of testosterone (androgens) during pregnancy causes poor development of male sexual characteristics.
  • Androgens causes muscular growth, facial and axillary hair growth, development of low pitch voice, aggression etc.
  • At puberty testosterone required for libido (male sexual behaviour), and erectile function.
  • Androgens stimulates spermatogenesis (Sperm formation).

4.10.2 Estrogen

  • It is secreted from the granulosa cells of maturing follicles.
  • Estrogens causes development of female secondary sex organs and sexual characteristics.
  • It regulates female sexual behaviour.

4.10.3 Progesterone

  • It is secreted from the corpus luteum (remnants of ruptured follicle after ovulation).
  • Progesterone required for maintaining pregnancy.
  • Progesterone stimulate mammary alveoli development and milk secretion.

4.11 Some Other Hormones

4.11.1 Atrial Natriuretic Factor, ANF

  • It is synthesized and secreted from the cardiac atrial. It is a peptide hormone.
  • ANF acts on the tubules (several tubular segments) to inhibit sodium reabsorption.
  • It act on the renal blood vessels to increase glomerular filtration rate (GFR).
  • ANF also directly inhibits aldosterone secretion.
  • It dilates blood vessels and thereby reduces blood pressure.

All the above functions of ANF directly of indirectly reduces sodium reabsorption and increases its excretion.

4.11.2 Erythropoietin

  • It is a peptide hormone.
  • It is secreted by the juxtaglomerular cells of the kidney.
  • It’s synthesis is stimulated by androgens.
  • It stimulates erythropoiesis (RBC formation).

4.11.3 Gastrointestinal hormones; Gastrin, Cholecystokinin (CCK), Secretin, -Glucose-dependent insulinotropic peptide (GIP)

  • All of these are peptide hormones.
  • Gastrin is produced in antrum of stomach and the rest three are produced in the small intestine.
  • Gastrin stimulates acid secretion in stomach, growth and motility of stomach and small intestine. It also stimulates growth of exocrine pancreas.
  • CCK inhibits acid secretion and motility of stomach, stimulates enzyme secretion from pancreas and growth of exocrine pancreas. It also stimulates contraction of gall bladder.
  • Secretin inhibits secretion from stomach and its motility. It stimulates growth of exocrine pancreas and bicarbonate secretion from pancreas.
  • GIP inhibits gastric secretions and motility. It also stimulates insulin secretion from pancreas.

5. Mechanism of Hormone Action

Different types of hormones acts differently. All cells do not contains receptor for all hormones. The cell which contain the receptor (either on the cell or inside the cell) are called target cell of the particular hormone. Like insulin acts on adipocytes and hepatocytes but not on other cells.

  • The receptors for the steroid and thyroid hormones reside inside the cell while for peptide hormones and catecholamines receptors lie on the plasma membrane.
  • Peptide hormones and catecholamines bind to the receptor on plasma membrane and activates one or more of the signal transduction pathways; the result is altered membrane potential or activity of proteins in the cell.
  • Intracellular receptors activated by steroid and thyroid hormones function as transcription factors. They combine with DNA in the nucleus and inducing the transcription of DNA into mRNA; the result is increased synthesis of particular protein. The mechanism of hormone action schematically represented in the figure given below.

6. Diabetes

Diabetes is disease in which blood sugar level of the sufferer rises. The normal blood sugar level is 90-130 mg per 100 ml of blood. In diabetics the sugar level maintained at a higher level. Diabetes mellitus and diabetes insipidus are two main types of diabetes.

  • Diabetes mellitus or “sugar diabetes” characterized by increase in blood sugar level. It results due to either loss of insulin production or loss of sensitivity of the target cells.
  • If insulin is not produced or produced in insufficient quantity by the β cells of pancreas, it results into type 1 diabetes mellitus.
  • If insulin is produced in sufficient quantity by the β cells of pancreas, but the target cells of the hormone insulin are hyporesponsive it results into type 2 diabetes mellitus.
  • Diabetes insipidus is caused by failure to produce vasopressin from the posterior pituitary (central diabetes insipidus), or the inability of the kidney to respond to vasopressin (nephrogenic diabetes insipidus). Both results into excessive water loss as urine (diuresis).

References:

  • Hall, J. E., PhD. (2015). Guyton and Hall Textbook of Medical Physiology. Elsevier Health Sciences.
  • Widmaier, E. P., Raff, H., & Strang, K. T. (2003). Vander et Al’s Human Physiology: With OLC Bind-In Card. McGraw-Hill Science, Engineering & Mathematics.
  • Fox, S. I., & Rompolski, K. (2021). ISE Human Physiology.

  • Diabetes (who.int)

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