- Slides: 25
COMPARATIVE STUDY OF HORMONES LECTURER IN CHARGE BAMIDELE OLUBAYODE
INTRODUCTION • The field of endocrinology is concerned with the study of hormones and their actions. • It is rooted in the comparative study of hormones in diverse species which has provided the foundation for the modern fields of evolutionary, environmental and biomedical endocrinology.
COMPARATIVE ENDOCRINOLOGY • Deals with identification of new hormones, hormone receptors and mechanisms of hormone action applicable to diverse species including humans. • Studies the impact of habitat destruction, pollution and climatic change on populations of organisms. • Establishes novel model systems for studying hormones and their functions. • Develops new genetic strains and husbandry practices for efficient production of animal protein.
HISTORY OF COMPARATIVE STUDY OF HORMONES • This is dated to the early part of the 20 th century, when the field of endocrinology first began. • Research in endocrinology was almost exclusively associated with Medical Schools before 1940. • The comparative study of animal hormones developed with the expansion of the field of Zoology during 1940 s and 1950 s. • Comparative endocrinology was born in 1954 with the First International symposium held on it at liverpool, England.
FIELDS RELEVANT TO COMPARATIVE ENDOCRINOLOGY • Advances in Biochemistry, Molecular Biology and Genetics have brought startling advances in our understanding of animal hormones and their actions.
CONTRIBUTIONS OF COMPARATIVE ENDOCRINOLOGISTS TO BIOMEDICAL RESEARCH 1. Arnold Adolph of University of Gottingen reported in 1849 the first endocrinological experiment in which he castrated cockerels and found that this caused regression of secondary sex characters, such as wattles and comb, and the loss of male -typical sexual behaviour (Barthold, 1849)
CONTRIBUTIONS OF COMPARATIVE ENDOCRINOLOGISTS TO BIOMEDICAL RESEARCH 2. The term 'hormone' was first coined by Ernest Sterling, who together with his brother-in-law, William Baylis, found that the upper part of the dog's small intestine, the duodenum produced a substance called Secretin that stimulated secretion of pancreatic juice into the small intestine. This was the first demostration that factors transported via blood stream could act on other tissues and coordinate physiological functions(Henderson, 2005)
CONTRIBUTIONS OF COMPARATIVE ENDOCRINOLOGISTS TO BIOMEDICAL 3. In the 19 th century, the. RESEARCH role of the pituitary gland in growth of the body was suggested by post-mortem observation of human that suffered from acromegaly, but the first experimental evidence was the discovery made in the early 20 th century that pituitary extract caused growth of the gonads of frogs (Greep, 1988).
CONTRIBUTIONS OF COMPARATIVE ENDOCRINOLOGISTS TO BIOMEDICAL RESEARCH 4. Comparative studies played a key role in the development of the concept of neurosecretion and the field of neuroendocrinology. Ernst Sharrer first developed the concept of neurosecretion based on his work with the minnow, Phoximus laevis, in which he postulated that specific neurons in the preoptic nucleus of the hypothalamus possessed endocrine activity related to pituitary function (Klavdieva, 1995).
CONTRIBUTIONS OF COMPARATIVE ENDOCRINOLOGISTS TO BIOMEDICAL RESEARCH 5. Wolfgang Bargmann is credited with having firmly established the existence and functional role of neurosecretion in vertebrates (Klavdieva, 1995). 6. Babnado Houssay, working with toads, was the first to show that blood flowed from the hypothalamus to the pituitary gland (Houssay, 1935)
COMPARATIVE STUDY OF HORMONES AS EXEMPLIFIELD BY VASOPRESSIN • Neuropeptides and neuropeptide actions were first discovered in nonmammalian species that were subsequently found to play important roles in human physiology and disease state. • For example, the neuropeptide arginine vasotocin- AVT (the mammalian homolog is arginine vasopressin- AVP) was first found to influence reproductive behaviour in amphibians, and is now known to control social behaviour in diverse vertebrate species (Goodson and Bass, 2001)
COMPARATIVE STUDY OF HORMONES AS EXEMPLIFIELD BY VASOPRESSIN • Arginine-vasotocin (AVT)/ arginine-vasopressin (AVP) are members of the AVP/ Oxytocin (OT) superfamilyof peptides that are involved in the regulation of social behaviour, social cognition and emotion in a wide range of species. • AVT/AVP reproductive function was discovered over 70 years ago while the non-reproductive functions was as recent as 30 years ago.
COMPARATIVE STUDY OF HORMONES AS EXEMPLIFIELD BY VASOPRESSIN • The AVP/OT peptide superfamily evolved more than 600 million years ago from an ancestralform of AVT through gene duplication. • AVT/AVP are nonapeptides because the contain nine amino acid residues. • AVT Is found in fish, amphibians, reptiles and birds while AVP or AVP-like peptide (e. g lysine vasopressin) occur in mammals.
COMPARATIVE STUDY OF HORMONES AS EXEMPLIFIELD BY VASOPRESSIN NONAPEPTIDE RECEPTORS EXPRESSION V 1 a Many region of the mammalian brain V 1 b Brain, Hippocampus, Lower levels in the Hypothalamus and Amydala V 2 In the adult and developing mammalian brain OT Many region of the mammalian brain
COMPARATIVE STUDY OF HORMONES AS EXEMPLIFIELD BY • Recent discoveries implicated AVP in human pair bonding VASOPRESSIN (Walum et al, 2008) and mental health disoder such as autism. (Wassink et al, 2004).
COMPARATIVE STUDY OF HORMONES AS EXEMPLIFIELD BY GASTRIN • Gastrin is released from G cells in the antral mucosa in response to nutrients, and stimulates acid secretion in the gastric mucosa. In addition, gastrin is associated with the growth and differentiation of the gastric mucosa. • Gastrin was first purified from pig antral mucosa, and identified as two types of 17 aa peptides, in 1964. One peptide is O-sulfated on the tyrosine located at the sixth residue from the C-terminus (G 17 -II). The other peptide is not sulfated(G 17 -I)
COMPARATIVE STUDY OF HORMONES AS EXEMPLIFIELD Structure BY GASTRIN • Human preprogastrin is composed of 101 aa residues. Three mature peptides with different N-terminal extensions, big gastrin (G 34), little gastrin (G 17), and small gastrin (G 14), are formed by posttranslational processing. • Furthermore, non-amidated glycine-extended gastrin is found in blood and tissues. Human G 17 contains a pyroglutamicacid residue in the N-terminus, and is amidated at the C-terminus. In mammals, all gastrins possess a sulfated Tyr located as the sixth residue from the C-terminus.
COMPARATIVE STUDY OF HORMONES AS EXEMPLIFIELD GASTRIN Synthesis and. BY Release • The human gastrin gene (GAS), located on chromosome 17 (17 q 21), consists of three exons. The gene structure of gastrin is conserved in mammals, except for that of porcine. • Gastrin, which has five exons. In mammals, the latter two exons are the coding region of the gastrin gene. GAS m. RNA is a 475 -bp transcript that encodes the 101 -aa preprogastrin protein.
COMPARATIVE STUDY OF HORMONES AS EXEMPLIFIELD BY GASTRIN Biological Functions Gastrin is released into the blood stream from antrum G cells, and induces the synthesis and release of histamine from enterochromaffin-like cells (ECL cells) through CCK 2 R. Histamine binds to histamine-2 receptors and stimulates acid secretion in parietal cells. Furthermore, gastrin directly activates acid secretion in parietal cells via CCK 2 R. Studies of the mouse model of hypergastrinemia and genetically modified mice have demonstrated that gastrin is responsible for normal growth and differentiation of the gastric mucosa.
COMPARATIVE STUDY OF HORMONES AS EXEMPLIFIELD BY GASTRIN Phenotype in Gene-Modified Animals • Gastrin gene knockout mice exhibit achlorhydria and atrophy of the gastric mucosa because of reduction of the parietal cell mass and non-activation of ECL cells. Bacterial overgrowth is observed in the stomachs of gastrin-deficient mice. Cck 2 r-deficient mice show 10 -fold higher plasma concentrations of gastrin compared with wild-type mice. In addition, chlorhydria and hypoplasia of the oxyntic mucosa is observed in Cck 2 r null mice. Investigations using electron microscopy to study Cck 2 r-deficient mice report abnormal ECL cell differentiation.
COMPARATIVE STUDY OF HORMONES AS EXEMPLIFIELD BY • Thyroid hormones (THs), thyroxine (T 4) and THYROXINE triiodothyronine (T 3), are known regulators of growth, metabolism and reproduction in many vertebrates. • These effects are also transmitted across generations in that THs play a critical role in early development in the offspring. • Their role in early development and metamorphosis is well established in mammals and amphibians, respectively, and recently several studies in fish have highlighted the importance of THs during flatfish metamorphosis.
COMPARATIVE STUDY OF HORMONES AS EXEMPLIFIELD BY THYROXINE • THs are present in high quantities in fish eggs and are presumably of maternal origin. • During embryogenesis the concentration of T(4) and T(3) in the eggs decrease until endogenous production starts. • Thyroid hormone receptors (TR) have been isolated from several teleosts and in common with tetrapods two receptor isoforms have been identified, • TR alpha and TR beta. Both the receptors are expressed in early embryos and larvae of the Japanese flounder
COMPARATIVE STUDY OF HORMONES AS EXEMPLIFIELD BY THYROXINE • Thyroid hormones and TRs are important in fish embryogenesis, larval development and during metamorphosis. • Thyroid hormone is also necessary for controlling amphibian metamorphosis. • It is implicated in development of young and adult reptiles.
REFERENCES • Robert et al. (2009). Comparative endocrinology in the 21 st Century. Integrative and Comparative Biology. 49(339 -348). • Gardner Lynn and Henry E. Wachowsk. (1951). The Thyroid Gland Its Functions in Cold-Blooded Vertebrates. W. i. The Quarterly Review of Biology. Vol. 26, No. 2, pp. 123 -168. • Power et al. (2020). Thyroid hormones in growth and development of fish. Comparative_Biochemistry_and_Physiology_Part_C_Toxi cology_Pharmacology. Vol 130(4): 447 -59.
THE END THANK YOU FOR ATTENTION