Gastrointestinal Hormones
Considered as the only site for nutrient assimilation, the gastrointestinal tract (GIT) also produces hormones that are responsible for regulating secretions of exocrine glands, gastrointestinal motility, cellular proliferation, and differentiation in GIT.
The first hormone to be discovered by Bayliss & Starling (1902) is secretin, which is a gut hormone.Considered the largest endocrine organ in the animal’s body, GIT produces more than 20 peptide hormones.
17.4.1 Properties of the Gut Hormones
The hormone-producing cells are also known as the enteroendocrine cells (EECs), interspersed between gut mucosal cells in GIT. They are derived from the pluripotent intestinal stem cells in the intestinal crypts. Different types of EECs are present in the GIT, with each cell type having the ability to synthesize and secrete at least one kind of hormone (Table 17.2). The hormones thus produced can also act as autocrine or paracrine or neurocrine factors on the nearby target cells. Based on the structural homologies, the gut hormones are further classified into different families: the secretin family (secretin, glucagon-like peptides, VIP), the
Table 17.2 Source, chemical structure, receptors of different GIT hormones and their effect on feed intake in animals
| S. No | Hormone | Cell type and location | Chemical structure | Receptor | Feed intake |
| 1. | Gastrin | G cell (Stomach, duodenum) | 34 aa—Big gastrin 17aa—Little gastrin 14aa—Small gastrin | CCK2R (Gq type) | |
| 2. | CCK (Pancreozymin) | I/L cells (Small intestine) | 33 aa | CCK1R (Gq type) | |
| 3. | Ghrelin | A (X-like) cell (Stomach) | 28 aa | GHS-R1a/ GHS-R1b (Gq type) | ↑ |
| 4. | Motilin | M cell (Duodenum) | 22 aa | MTLR | ↑ |
| 5. | Secretin | S cells (Small intestine) | 27 aa | SCTR (Gs type) | |
| 6. | Vasoactive intestinal polypeptide (VIP) | Myenteric and submucosal neurons | 28 aa | VPAC-I/ VPAC-II (Gs type) | |
| 7. | Gastric inhibitory polypeptide (GIP) | K cell (Duodenum) | 42 aa | GIPR (Gs type) | |
| 8. | Glucagon-like peptide-1 (GLP-1) | Lcell (Ileum, colon) | 31 aa | GLP-1R (Gs type) | |
| 9. | Glucagon-like peptide-2 (GLP-2) | Lcell (Ileum, colon) | 33 aa | GLP-2R (Gs type) | |
| 10. | Oxyntomodulin (OXM) | Oxyntic cells (Fundus) | 37 aa | GLP-1R (Gs type) | |
| 11. | Gastrin-releasing peptide (GRP)/ Bombesin-like peptide | Stomach, small intestine (Neuropeptide) | 27 aa | GRPR (Gq type) | |
| 12. | Neuropeptide Y (NPY) | Neuropeptide (Expressed primarily in CNS, also released in GIT) | 36 aa | Y1-6 (Gi type) | ↑ |
| 13. | Peptide YY (PYY) | L cell (Jejunum, caecum, colon) | 36 aa | Y1, Y2, Y5 (Gi type) | |
| 14. | Somatostatin | D cell (Stomach, small intestine) | 28 aa (SS-28) 14 aa (SS-14) | SSTR (Gi type) | |
| 15. | Enteroglucagon | Lcell | 29 aa | GCGR (Gs & Gqtype) | |
| 16. | Leptin | Stomach, adipose tissue | 167 aa | Lep-R |
Gq type G-protein coupled receptor that activates PLC; Gs type G-protein coupled receptor that activates AC; Gi type G-protein coupled receptor that inhibits AC
gastrin family (gastrin, CCK), and the PP-fold family (Neuropeptide Y (NPY), PYY, pancreatic polypeptide).
17.4.2 Biological Effects
The gut hormones have a unique property of activating at least one specific type of GPCR present on the target tissues. The signal transduction mechanisms include the activation of adenylyl cyclases, protein kinases, and membrane-bound ion channels. With overlapping target organs, multiple gut hormones are needed to produce the desired biological effects. The major biological effects of gut hormones include the regulation of ingestion, digestion, and metabolism of nutrients (Table 17.3).
17.4.2.1 Effects on Feed Intake
Based on their ability to stimulate or inhibit the intake of feed, they are classified as orexigenic and anorexigenic hormones, respectively. Orexigenic hormones like ghrelin, motilin, and insulin-like peptide 5 (INSL5) are secreted at a maximum rate before feeding to initiate hunger sensation. Whereas, presence of nutrients in the GIT induces the release of anorexi- genic hormones such as cholecystokinin (CCK), glucagon-
Table 17.3 Biological effects and the regulation of secretion of gut hormones
| S. No | Hormone | Biological effects | Stimulus | Inhibition |
| 1. | Gastrin | • Stimulates gastric acid secretion • Antagonistic to GIP and Secretin • Growth and differentiation of gastric mucosa | • Gastrin-releasing peptide (GRP), • Amino acids | Somatostatin, ↑H+ ion concentration |
| 2. | CCK (Pancreozymin) | • Contraction of gall bladder • Relaxation of the sphincter of Oddi • Enzyme rich pancreatic secretion | • Dietary lipids and amino acids | Somatostatin, pancreatic peptide |
| 3. | Ghrelin | • Increase gastric acid • Increase gastric emptying • Increase GH • Decrease insulin | • Feed deprivation | Substance P |
| 4. | Motilin | • Increases intestinal motility • Migrating myoelectric complex | • Cyclical pattern of release (90 min interval) | Ingestion of feed |
| 5. | Secretin | • Inhibits gastric acid release • Inhibits gastric emptying • Stimulates bicarbonate rich pancreatic secretion | • Presence of gastric acid in duodenum • Digestive by-products of fats and proteins | Somatostatin |
| 6. | Vasoactive intestinal polypeptide (VIP) | • Inhibits gastric acid secretion • Relaxation of intestinal smooth muscle • Stimulates secretion of anions (Cl-, HCO3-)in the intestine, insulin, and glucagon from the pancreas • Potent vasodilator | • Serotonin, • Acetylcholine (ACh), • Substance P (Enteric neurons) | Somatostatin |
| 7. | Gastric inhibitory polypeptide (GIP) | • Stimulates insulin secretion • Induces satiety • Decreases gastric acid and gastric emptying | • Presence of fats and carbohydrates in the intestine | Somatostatin |
| 8. | Glucagon-like peptide-1 (GLP-1) | • Induces satiety • Decreases gastric motility • Stimulates insulin secretion • Suppress glucagon secretion | • Carbohydrates and lipids in the ration • Leptin • GIP | Insulin |
| 9. | Glucagon-like peptide-2 (GLP-2) | • Control growth and function of GIT by regulating epithelial integrity, secretion, blood flow, and motility | • Dietary carbohydrates and lipids, • GIP | Somatostatin |
| 10. | Oxyntomodulin | • Stimulates insulin release • Increases satiety • Decreases gastric acid • Increases energy expenditure • Lipolysis | • Response to feed intake | |
| 11. | Gastrin-releasing peptide (GRP)/Bombesin-like peptide | • Increases gastrin secretion • Regulate food intake • Male sexual functions • Memory consolidation | • Gastric phase of digestion (Vagal stimulation) | - |
| 12. | Neuropeptide Y (NPY) | • Induces food intake • Lowers energy expenditure • Circadian rhythm | • Low energy status | Leptin |
| 13. | Peptide YY (PYY) | • Reduces gastric acid secretion, • Decreases gastric emptying • Inhibits appetite | • Dietary fats | Obesity |
| 14. | Somatostatin | • Inhibits the release of GH, CCK, gastrin, motilin, secretin, GIP, VIP, etc. | • Increased uptake of nutrients | GH, IGF-1 |
| 15. | Enteroglucagon | • Increase enterocyte proliferation | • Feed intake | Increased blood glucose |
| 16. | Leptin | • Decrease feed intake • Increase energy expenditure | • Increase adipose tissue (Positive energy balance) | Decreased fat tissue (Negative energy balance) |
like peptide 1 (GLP1), peptide YY (PYY), and oxyntomodulin that stimulate the cessation of feed intake and cause satiety.
17.4.2.2 Effects on Digestion
The gut hormones modulate the secretion of bile, gastric acid, pancreatic enzymes, and bicarbonate ions to provide an ideal environment for the enzymatic breakdown of complex feeds ingested by the animal into simpler nutrients.
In addition, they determine the rate of gastric emptying and motility patterns of the intestine, thereby providing appropriate time for digestion, absorption, and elimination of indigested feed.17.4.2.3 Effects on Metabolism
Together the gut hormones regulate energy homeostasis by affecting the secretion of hormones and metabolic pathways The GLP1, oxyntomodulin, and gastric inhibitory peptide (GIP) prevent hyperglycemia by stimulating the secretion of insulin from the pancreas, hence known as incretins. On the other hand, ghrelin stimulates growth hormone secretion from the anterior pituitary and increases adipogenesis and circulatory glucose levels. In addition, hormones such as CCK and GLP1 cause meal-induced thermogenesis by stimulating lipolysis of brown adipose tissue (BAT).
17.4.2.4 The Gut-Brain Axis
The EECs play the role of nutrient sensing and produce hormones that help to relay the sensory information so accrued to various parts of the brain. Subsequently, the higher regulatory centers respond by regulating various physiological functions, especially the animal’s appetite, thus forming a gut-brain axis.
17.4 Placental Hormones
The placenta acts as the site of attachment of the fetus, delivers nutrients and gases derived from maternal circulation, prevents the fetal allograft from the maternal immune system, and eliminates fetal metabolic-waste products. In addition, it acts as a transient endocrine organ by producing hormones that are vital for the maintenance of gestation, fetal growth, and parturition.
17.5.1 Progesterone
Progesterone stands as an absolute requirement for the maintenance of gestation in all mammals. Although corpus luteum is the primary source of progesterone in domestic animals, placental-derived progesterone also helps in the maintenance of gestation. The shift of progesterone production from the corpus luteum to the placenta is regarded as an essential phenomenon seen in the case of equines, sheep, and primates.
This luteo-placental shift in progesterone synthesis has minor relevance in goats and pigs. Luteal-progesterone plays a prominent role in myometrial quiescence, endometrial growth and differentiation, immunosuppression to prevent fetal rejection, and cervical closure. However, the progesterone derived from the placenta is speculated to be useful for species with longer gestation.17.5.2 Estrogen
Unlike follicle that produces 17β-estradiol, placenta in ungulate animals primarily secretes estrone in sulfate form. In primates, placental estrogen is implicated in trophoblast differentiation, mammary gland development, and uteroplacental blood flow. However, in cattle, maternal estrogen levels rise along with a concomitant decrease in progesterone levels at the end of gestation period due to an increased conversion of progesterone to estrogen by CYP17A1 (17- α-hydroxylase) in the placenta. Thus, the increased circulatory levels of estrogen lead to the ductular development of the mammary gland, remove the progesterone-mediated negative feedback on lactation, excite the myometrial tissue, and prepare the birth canal for parturition.
17.5.3 ChorionicGonadotropins
As of now, only two chorionic gonadotropins: equine chorionic gonadotropin (eCG) and human chorionic gonadotropin (hCG) are reported in equines and primates, respectively. Like the pituitary gonadotropins (LH & FSH), the chorionic gonadotropins are made of a common α-glycoprotein chain. However, β-chains of chorionic gonadotropins (βCG) are similar to the βLH chain, except that they are heavily glycosylated. The hCG released by blastocyst in primates is responsible for the maternal recognition of pregnancy and maintenance of corpus luteum by binding to LH receptors. Whereas, distinct areas of the placenta known as endometrial cups secrete eCG to promote the formation of accessory corpora lutea, thereby helping in the maintenance of gestation.
17.5.4 Placental Lactogen (Chorionic Somatomammotropin)
The binucleate cells of trophectoderm in ruminants, primates, and rodents secrete placental lactogen, a hormone that has both somatotropic and lactogenic functions. Mature placental lactogen (PL) is a single polypeptide chain with 200 amino acids. In bovines, PL shares a structural homology of 50% and 23% with PRL and GH, respectively. The circulatory levels of PL start raising from Day 30 onwards, reaching a peak during the last trimester, and begin to fall when the animal approaches parturition. In ruminants, PL has luteotro- phic actions and augments progesterone secretion from the corpus luteum. It plays a major role in the partitioning of maternal nutrients to support fetal growth by stimulating the uptake of maternal nutrients, and glycogenesis in fetal tissues. In addition, it stimulates lobuloalveolar growth in the mammary gland and exerts galactopoietic effects by stimulating dry matter intake.
17.5.5 Relaxins
They are peptide hormones belonging to the insulin family, produced primarily by the corpus luteum and placenta. Relaxin1 (RLN 1) plays a major role in reproductive functions in mammals. It is a polypeptide heterodimer hormone with 53 amino acids. The production of RLN1 rises at the end of gestation to promote cervical ripening, dilatation of pubic symphysis, and relaxation of the sacrosciatic ligament to aid the process of parturition.
Know More...
• The long half-life and potent FSH-like activity of eCG make it an ideal hormone used for multiple ovulation protocols/embryo transfer protocols in cattle and buffaloes.
• Since eCG is found in pregnant mares, it is also known as pregnant mare serum gonadotropin (PMSG).
17.5