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Paper : 06 Animal Physiology Module : 19 Pituitary

Development Team

Principal Investigator: Prof. Neeta Sehgal Department of Zoology, University of Delhi

Co-Principal Investigator: Prof. D.K. Singh Department of Zoology, University of Delhi

Paper Coordinator: Prof. Rakesh Kumar Seth Department of Zoology, University of Delhi

Content Writer: Dr. Meena Yadav Maitreyi College, University of Delhi

Content Reviewer: Prof. Neeta Sehgal Department of Zoology, University of Delhi .

Animal Physiology ZOOLOGY Pituitary

Description of Module

Subject Name ZOOLOGY

Paper Name Zool 006 Animal Physiology

Module Name/Title Neuro-endocrine Physiology

Module Id M19 Pituitary hormone

Keywords Adenohypophysis, neurohypophysis, median eminence, endocrinokinetic hormones, supraoptic nucleus, paraventricular nucleus, (POMC), magnocellular neurons, neurophysin, Herring bodies

Glossary: 1. Hypophysis: Another name of pituitary gland which secretes several hormones 2. Adenohypophysis: Also called as and secretes six major hormones i.e. ACTH, GH, FSH, LH, PRL and TSH 3. Neurohypophysis: also called as and secrets two major hormones i.e. and or Antidiuretic hormone (ADH) 4. Portal capillary plexus: A close network of capillaries in median eminence where anterior pituitary secretes its hormones which then go in general circulation. 5. Tropic hormones or endocrinokinetic hormones: The hormones which stimulate other endocrine glands to secrete hormones. For example, anterior pituitary hormones. 6. Adrenocorticotropic hormone (ACTH): It is also known as corticotropin. It stimulates the production and secretion of hormones from adrenal cortex. 7. Corticotropin Releasing Hormone (CRH): It is secreted by and stimulates the release of ACTH by anterior pituitary. 8. Proopiomelanocortin (POMC): It is a preprohormone which when processed gives rise to several hormones like ACTH, Stimulating Hormone (MSH), β-lipotropin, and β- endorphin. 9. (GH): It is also known as somatotropin or somatotropic hormone (STH). It stimulates body to grow by acting mostly on skeleton and skeletal muscles. GH has important role in during neonatal and postnatal growth and puberty.

Animal Physiology ZOOLOGY Pituitary hormones

10. Growth Hormone Releasing Hormone (GHRH): It stimulates the release of GH from anterior pituitary. 11. Growth Hormone Inhibiting Hormone (GHIH) or : It inhibits the release of GH from anterior pituitary. 12. Somatotrophs: These are specialized cells in anterior pituitary which secrete GH. 13. Stimulating Hormone (TSH): It acts on thyroid gland and stimulates the release of T3 and T4. 14. Thyrotropin Releasing Hormone (TRH): It is also called as Thyroid Stimulating Hormone Releasing Hormone (TSHRH) and stimulates the release of TSH from anterior pituitary. 15. Thyrotrophs: These are specialized cells in anterior pituitary which secrete TSH. 16. : It is a general term used for hormones which act on gonads. Examples of gonadotropins are LH and FSH. 17. Gonadotrophs: Specialized cells in anterior pituitary which secrete gonadotropins 18. Releasing Hormone (GnRH): This hormone is secreted by hypothalamus which further stimulates secretion of gonadotropins from anterior pituitary 19. Follicle Stimulating Hormone Releasing Hormone (FSHRH): It is a type of GnRH and stimulates release of FSH from anterior pituitary. 20. Releasing Hormone (LHRH): It is a type of GnRH and stimulates the release of LH 21. Inhibin B: It is a glycoprotein produced by gonads which inhibits the secretion of FSH. 22. Inhibiting Hormone (PIH) or : It regulates the secretion of prolactin from anterior pituitary. 23. Lactotrophs: The specialized cells in anterior pituitary which secrete prolactin 24. Magnocellular neurons: These neurons are large having large cell bodies of 20-40 µm diameter and are secretory by nature. 25. Parvocellular neurons: The neurons whose cell bodies have diameter of 10-15 µm and they are also neurosecretory. 26. Supraoptic Nucleus: The area in hypothalamus which secretes vasopressin 27. Paraventricular Nucleus: The area in hypothalamus which secretes oxytocin 28. Neurophysin: It is a protein which binds oxytocin and vasopressin. 29. Prepropressophysin: It is precursor molecule for vasopressin

Animal Physiology ZOOLOGY Pituitary hormones

30. Prepro-oxyphysin: It is precursor molecule for oxytocin 31. Herring bodies: These are secretory granules which contain precursor molecules for oxytocin and vasopressin.

Selected References:

1. Larry Squire, Darwin Berg, Floyd Bloom, SaschaduLac, Anirvan Ghosh and Nicholas Spitzer. Fundamental Neuroscience. 3rd Edition (2008). Academic Press 2. Ganong’s Review of Medical Physiology. 23rd Edition (2010). 3. Ganong’s Review of Medical Physiology. 25th Edition (2016). 4. Guyton and Hall. Textbook of Medical Physiology. 11th Edition (2006). 5. Carolina Perez-Castro, Ulrich Renner, Mariana R. Haedo, Gunter K. Stalla, Eduardo Arzt (2012). Cellular and Molecular Specificity of Pituitary Gland Physiology. Physiological Reviews, Vol. 92(1): 1-38 6. Aguilera G, Rabadan-Diehl C (2000). Vasopressinergic regulation of the hypothalamic- pituitary-adrenal axis: implications for stress adaptation. Regul Pept 96: 23–29, 2000 7. https://www.ncbi.nlm.nih.gov/books/NBK29/ 8. https://www.ncbi.nlm.nih.gov/books/NBK26/ 9. https://www.ncbi.nlm.nih.gov/books/NBK27/ 10. https://www.ncbi.nlm.nih.gov/books/NBK278958/ 11. Shupnik, M.A., Ridgway, E.C. & Chin, W.W. (1989). Molecular biology of thyrotropin. Endocr Rev, 10, 459-475. 12. Grossmann, M., Weintraub, B.D. & Szkudlinski, M.W. (1997). Novel insights into the molecular mechanisms of human thyrotropin action: structural, physiological, and therapeutic implications for the glycoprotein hormone family. Endocr Rev, 18, 476-501. 13. Wang HC and Klein JR (2001). Immune function of thyroid stimulating hormone and receptor. Crit Rev Immunol, 21(4):323-37. 14. Mariusz W. Szkudlinski, Valerie Fremont, Catherine Ronin and Bruce D. Weintraub (2002). Thyroid stimulating hormone and thyroid stimulating hormone receptor structure-function relationship. Physiol Reviews, 82(2):473-502.

Animal Physiology ZOOLOGY Pituitary hormones

15. Michael P. Mullen, ara J. Cooke and Mark A. Crow. Structural and functional roles of FSH and LH as glycoproteins regulating reproduction in mammalian species. Gonadotropin, edited by Jorge Vizcarra (ISBN: 978-953-51-1006-4). 16. Freeman ME, Kanyicska B, Lerant A and Nagy G (2000). Prolactin: Structure, function and regulation of secretion. Physiol Rev, 80(4): 1523-631. 17. Anne Bachelot and Nadine Binart (2007). Reproductive role of prolactin. Reproduction, 133: 361-369. 18. Carolina Perez-Castro, Ulrich Renner, Mariana R. Haedo, Gunter K. Stalla, Eduardo Arzt (2012). Cellular and Molecular Specificity of Pituitary Gland Physiology. Physiological Reviews, Vol. 92(1): 1-38.

Animal Physiology ZOOLOGY Pituitary hormones

Value addition: Fact file Heading title: Major Depression and its connection with ACTH

Body Text: Major depression (MD) is a severe, life-threatening, and widespread psychiatric disorder and is also a risk factor for cardiovascular and metabolic diseases, and a major risk factor for suicide. Stress is actually a state of disturbed homeostasis which induces some somatic and mental adaptive reactions, to restore the initial homeostasis or reach a new level of homeostasis.The stress response has been linked to the HPA axis. van der Laan et al., have demonstrated that if glucocorticoid receptors are activated, the cAMP-induced transcription of CRH gene is decreased or inhibited. Thus, in vivo, there is a critical time window which significantly inhibits the CRH gene and ACTH gene, via HPA axis, due to glucocorticoids. In all MD cases, a minor role of HPA axis is always there which is visible either at baseline or with functional tests. The biomarkers of stress response in preclinical models of MD usually are increased circulatory hormones like adrenocorticotropic hormone (ACTH) or /corticosterone and increased the weight of . References 1. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0004265 2. van der Laan S, de Kloet ER, Meijer OC (2009) Timing is critical for effective glucocorticoid receptor-mediated repression of the cAMP-induced CRH gene. PLoS ONE 4(1): e4327.S. van der LaanER de KloetOC Meijer2009Timing is critical for effective glucocorticoid receptor- mediated repression of the cAMP-induced CRH gene.PLoS ONE4(1)e4327 3. Cryan JF, Mombereau C (2004) In search of a depressed mouse: utility of models for studying depression-related behavior in genetically modified mice. Mol Psychiatry 9: 326–357.JF CryanC. Mombereau2004 In search of a depressed mouse: utility of models for studying depression-related behavior in genetically modified mice.Mol Psychiatry9326357

Animal Physiology ZOOLOGY Pituitary hormones

Value addition: Fact file

Heading title: FSH levels during folliculogenesis

Body Text:

Threshold FSH and its levels during folliculogenesis:

The follicles at different stages are differentially sensitive to the FSH levels. For example, the early antral stage needs the highest amount of FSH and it declines during late antral stage. The follicle which has highest sensitivity will become dominant during development and maturation.

References: 1. GottumukkalaAchyuta Rama Raju, Rahul Chavan, MamtaDeendayal, DevikaGunasheela, RohitGutgutia, GeethaHaripriya,MirudhubashiniGovindrajan, Nayana Hitesh Patel and AmeetShashikantPatki (2013). Luteinizing hormone and follicle stimulating hormone synergy: A review of role in controlled ovarian hyper-stimulation. J Hum ReprodSci; 6(4): 227–234. 2. Sullivan MW, Stewart-Akers A, Krasnow JS, Berga SL, Zeleznik AJ. Ovarian responses in women to recombinant follicle-stimulating hormone and luteinizing hormone (LH): A role for LH in the final stages of follicular maturation. J ClinEndocrinolMetab. 1999;84:228–32.

Animal Physiology ZOOLOGY Pituitary hormones

Value addition: Fact File Heading Title: Polycystic Ovarian Syndrome (PCOS) and gonadotropins

Body Text: In women with PCOS, the amplitude and frequency of LH and FSH secretion are more as compared to women with normal cycles, during entire folliculogenesis phase. In approximately 40% of PCOS women, excess amount of LH is secreted. The interaction of FSH with its receptors is crucial for development and maturation of follicles, so if there are any changes in the receptors, the signaling pathways are disturbed and hence, the folliculogenesis.75% cases of infertility are due to an ovulatory PCOS condition, which increases the risk of infertility and miscarriages.

The shape of polycystic is different than the normal ovaries and the size is almost two times more with voluminous stroma.

References: 1. Amir HosseinHashemi, HosseinMozdarani and AnooshNaghavi (2016). Comparison of the Levels of LH and FSH, TSH, Prolactin, and Hormones between Iranian Infertile Women with Polycystic Syndrome and Healthy Women. International Journal of Medical Research & Health Sciences, 5, 12:370-375

Value addition: Fact File Heading Title: Oxytocin and AutismSpectrum Disorders (ASD)

Body Text: Oxytocin has been known to play role in social recognition, attachment and stereotyped behaviors. The children with autism have lower mean plasma levels of oxytocin while some reports also say that adults with ASD have increased basal levels of oxytocin in plasma. This indicates that there might be some alterations during the processing of oxytocin which accounts for the symptoms associated with ASD.

In the Caucasian ASD probands, the common mutation found in oxytocin gene (OXT) is: OXT (2 SNPs) and mutation in its receptor are: OXTR (3 SNPs).Oxytocin is also known to have a role in schizophrenia, mood disorders, bipolar disorders, anxiety, Obsessive-Compulsive disorder,

Animal Physiology ZOOLOGY Pituitary hormones

personality disorders etc.

References: 1. David Cochran, Daniel Fallon, Michael Hill, Jean A. Frazier (2013). The role of oxytocin in psychiatric disorders: A review of biological and therapeutic research findings. Harv Rev Psychiatry. Harv Rev Psychiatry, Sep-Oct; 21(5): 219–247. 2. Modahl C, Green L, Fein D, et al.(1998). Plasma oxytocin levels in autistic children. Biol Psychiatry; 43(4):270–277 3. Jansen LM, Gispen-de Wied CC, Wiegant VM, Westenberg HG, Lahuis BE, van Engeland H. Autonomic and neuroendocrine responses to a psychosocial stressor in adults with autistic spectrum disorder. J Autism DevDisord. 2006;36(7):891–899. 4. Yrigollen CM, Han SS, Kochetkova A, et al. Genes controlling affiliative behavior as candidate genes for autism. Biol Psychiatry. 2008;63(10):911–916.

Value addition: Fact File Heading Title: Specialized hormone-secreting cells in anterior pituitary&Somatotroph axis regulation

Body Text: Cell Hormone % Cell Pathology

Lactotrophs PRL 15 Prolactinomas

Gonadotrophs LH 10 Usually silent adenomas

FSH

Thyrotrophs TSH 5 Plurihormonal

Somatotrophs GH 40–50 Acromegaly

Corticotrophs ACTH 15–20 Cushing's disease

Animal Physiology ZOOLOGY Pituitary hormones

The secretion of GH is under hypothalamic control through GHRH and somatostatin. GH stimulates secretion of IGF-1 in target tissues and IGF-1 regulates secretion of GH by a negative feedback mechanism. GH hormone secretion is also controlled by a variety of hormones involved in metabolism, cytokines during pubertal changes and physiopathological disturbances.

References: 1. Carolina Perez-Castro, Ulrich Renner, Mariana R. Haedo, Gunter K. Stalla, Eduardo Arzt(2012). Cellular and Molecular Specificity of Pituitary Gland Physiology. Physiological Reviews, Vol. 92(1): 1-38

Animal Physiology ZOOLOGY Pituitary hormones

Animal Physiology ZOOLOGY Pituitary hormones