ANAT243 L1 Reproductive and Developmental Biology PDF

Module 1: Control of Fertility (Dr Mike Pankhurst) Overview of the structure and function of Semester 2 male and female reproductive systems. Module 2: Establishment and Maintenance of Pregnancy (Prof Greg Anderson) The processes of...

Module 1: Control of Fertility (Dr Mike Pankhurst) Overview of the structure and function of Semester 2 male and female reproductive systems. Module 2: Establishment and Maintenance of Pregnancy (Prof Greg Anderson) The processes of fertilization, implantation, and adaptation to pregnancy and lactation. Module 3: Developmental Biology (Assoc Profs Tim Hore and Megan Wilson) Development of the organism, emphasizing the key developmental biology concepts.  ANAT243 Module 1: Control of Fertility Lecture 1/9: Reproductive Messengers Dr Mike Pankhurst Department of Anatomy ([email protected]) Lindo-Ferguson Rm 225 © The content and delivery of all resources in this course are copyrighted. This includes video and audio recordings, PowerPoints, lecture notes and handouts. You may access the materials provided for your private study or research but may not further distribute the materials for any purpose, or in any other form, whether with or without charge. 5  Module Objective To provide an overview of the: structure and function of male and female reproductive systems, and the hormones that regulate reproduction http://www.pdimages.com/web9.htm [Public domain] Figure from: Patton and Thibodeau. (2015) Anatomy and Physiology (9th Ed) Figure from: Seeley et al. (2003) Anatomy and Physiology (6th Ed) 6  Lecture 1: Reproductive Messengers Additional reading: Wheater’s Functional Histology (6th Edition): pages 318-322 Essential Reproduction (9th Edition): pages 13-33 7  Lecture 1: Reproductive Messengers After this lecture, you should be able to: Describe concepts of neuronal, endocrine, neuroendocrine, paracrine, autocrine and juxtacrine signals Understand the concept of hormone negative feedback Describe regulation of anterior and posterior pituitary hormone release Describe the synthesis of steroid and protein hormones, and the structure of the cells involved Describe how steroids and proteins are secreted 8  Part 1 Cell-to-Cell Communication 9  Communication between cells / pūtau Intercellular chemical signals: allow one cell to communicate with another (e.g. hormones / taiaki) can act over a range of distances Chemical signal Signal-releasing cell Target cell 10  How do cells / pūtau receive signals? Receptors are specific to a limited number of ligands. A cell can express hundreds of different receptor types. Receptors respond to external signals and send messages into the cytoplasm. Intracellular domains often activate a range of cytoplasmic proteins. Source: https://slcc.pressbooks.pub/collegebiology1/chapter/ligands-and-receptors/ 11  Juxtacrine signalling: Signals sent through cell contact Target: one specific cell Juxtacrine Figures modified from: Seeley et al. (2003) Anatomy and Physiology (6th Ed); Alberts et al. Molecular Biology of the Cell (4th Ed) 12  Autocrine and Paracrine: Interstitial fluid signalling Target: local cells Target: self Autocrine Paracrine Figures modified from: Seeley et al. (2003) Anatomy and Physiology (6th Ed); Franco et al. (2014) J Neurology and Neurological Disorders. 1(1):103. 13  Hormonal: Signalling through the blood Target: cells anywhere in the body Neuroendocrine Endocrine Target cells: express receptors for the hormone Figures modified from: Seeley et al. (2003) Anatomy and Physiology (6th Ed) 14 How many hormones / taiaki can you think of? 15  Part 2 Neuroendocrine System 16  Endocrine/neuroendocrine system Responsible for synthesis and secretion of hormones o Hormones enable one body system to regulate another system Transported around the body via the bloodstream to act on target organs The hypothalamus and pituitary gland / repe tupu are major regulators of the endocrine system In reproduction: Hypothalamic-Pituitary-Gonadal axis 17  Hypothalamus and Pituitary Gland / Repe Tupu Major regulatory centre for the endocrine system Interaction between nervous and endocrine systems Figure modified from: Johnson (2012) Essential Reproduction (7th Ed) 18  Pituitary Gland / Repe Tupu; hypophysis Hypothalamus Median eminence Made up of two discrete lobes with different embryological origin: Infundibulum Anterior pituitary (adenohypophysis, originates from pharynx) Posterior pituitary (neurohypophysis, originates from brain) Figure modified from: Young et al. Wheater’s Functional Histology 19  Pituitary Gland / Repe Tupu; hypophysis Hypothalamus Connected to Median eminence hypothalamus by infundibulum Infundibulum Portal blood supply delivers hypothalamic hormones to anterior lobe of pituitary gland Figure modified from: Young et al. Wheater’s Functional Histology 20  Hypothalamus and Posterior Pituitary Gland / Repe Tupu Neurons with cell bodies in the hypothalamus project directly to the posterior pituitary gland Secrete oxytocin and vasopressin from terminals Figure modified from: Seeley et al. (2006) Anatomy & Physiology (7th Ed) 21  Hypothalamus and Anterior Pituitary Gland / Repe Tupu Median eminence Neurons with cell bodies in the hypothalamus project to the median eminence Secrete releasing & inhibiting hormones from terminals into portal blood system, which act on anterior pituitary cells Anterior pituitary cells secrete hormones that travel around the body Figure modified from: Seeley et al. (2006) Anatomy & Physiology (7th Ed) 22 Homeostasis of hormone / taiaki levels Feedback regulation (usually negative feedback) Hypothalamus Releasing (or inhibiting) hormone e.g. gonadotrophin releasing hormone (GnRH) Anterior pituitary gland Trophic hormone e.g. gonadotrophins; luteinizing hormone (LH), follicle-stimulating hormone (FSH) Distal target organ / gland Hormone sex steroids (e.g. estrogen, testosterone) stimulatory inhibitory Other target tissues 23  Part 3 Steroid and Peptide Hormones 24  Hormones / Taiaki Different types of hormones with differing chemical composition Different types of hormone have different mechanisms of action 1. Steroid hormones 2. Protein and peptide hormones Figure from: https://2e.mindsmachine.com/figures/08/08.05.html 25  Steroid hormones Four major steroid families Progestogens (e.g. progesterone / taiaki tūmua) Androgens “sex steroids” (e.g. testosterone / taiaki tāne) Taiaki taihemahema Oestrogens / taiaki uwha (e.g. oestradiol-17β) Corticosteroids (e.g. cortisol) 26  scc = side chain Steroidogenic Pathways cleavage (p450 scc – cholesterol side- cholesterol s cc chain cleavage 0 P45 enzyme) pregnenolone progestagens Δ5 pathway Δ4 pathway Worth watching androgens https://youtu.be/TJf62Omf7Cw oestrogens Figure modified from: Johnson (2018) Essential Reproduction (8th Ed) 27  Steroid hormones are derived from cholesterol Sources of cholesterol – circulating cholesterol (transported by carrier proteins like LDL) – Acetate (cells can make cholesterol) – Stored in lipid droplets 3) Lipid droplets Pregnenolone produced in StAR mitochondrion 1) Low density Cholesterol lipoprotein (LDL) Sex steroids 2) Acetate produced in smooth endoplasmic reticulum (SER) Step 1 is make pregnenolone 28  Steroid hormone production StAR = steroidogenic acute regulatory protein – transport protein that transfers cholesterol into mitochondria Cholesterol to pregnenolone occurs in mitochondria – ‘rate-limiting’ step – cytochrome P450 side chain cleavage enzyme in mitochondria Other sex steroids produced in smooth endoplasmic reticulum Further steroidal modification Images from: Arukwe, A. Cell Biol Toxicol 24, 527–540 (2008). https://doi.org/10.1007/s10565-008-90Norman AW, and Litwack, G (1997) Steroid Hormones: Chemistry, Biosynthesis, and Metabolism. Chapter 2 from ‘Hormones’. Elsevier. 69-7 29  e g n e n o l o n e P450 scc pr androgens progestagen s d s o i e r s t o You need to learn the steps on t ic androgens slide 27, o r There will be specific examples c in upcoming lectures, You need to be aware that Figure modified from: Johnson (2018) Essential Reproduction (8th Ed) steroids synthesis is complex. 30  Steroid Secretion and Transport Goldman et al. (2017). Endocrine Reviews 38(4):302-324.) ‘Lipophilic’ - freely diffuse across lipid cell membranes Poorly soluble in aqueous fluids Carrier proteins in blood and extracellular fluid have hydrophobic regions that steroids can bind to. Examples: – Sex steroid binding globulin (SHBG) – Human serum albumin (HSA) A small proportion of steroids is always coming ‘off’ the carrier protein Steroid hormones are ‘made on-demand’ rather than being stored in the cell. Why do you think this is? 31  Steroid Secretion and Transport Steroids bind to nuclear hormone receptors Receptors are found in cytoplasm Translocate to the nucleus when bound to their steroid ‘ligand’ Complex can bind directly with DNA and act as transcription factor (Note: there are also membrane- bound steroid receptors) Figure from: https://2e.mindsmachine.com/figures/08/08.05.html 32  Protein and Peptide Hormones Hormones made up of peptides or proteins (e.g. GnRH) Synthesised in cells from amino acids Often produced as preprohormones – subsequent processing to produce mature hormone (often several steps) GnRH = Gonadotropin- releasing hormone Figure modified from: Johnson (2018) Essential Reproduction (8th Ed) 33  Protein and Peptide Hormones Mature hormones packaged into secretory vesicles that can be released into the blood stream Water-soluble (hydrophilic, lipophobic) What kind of receptors do you think protein/peptide hormones bind to? 34 Figure from: https://veteriankey.com/the-endocrine-system-2/  Protein and Peptide Hormones Cannot enter cells like lipids – have to bind to receptor on surface of target cells Receptor acts as transducer - sets off cascade of intracellular events The ‘second messenger’ systems needed to elicit response can be incredibly complex Figure from: https://2e.mindsmachine.com/figures/08/08.05.html 35  Steroid Peptide Synthesis Derived from cholesterol Made up of amino acids. Synthesised as preprohormones that require processing Storage Released immediately Stored in vesicles Solubility Require carrier proteins to Water soluble. travel in blood. Hydrophilic - cannot cross cell Lipophilic - can cross cell membrane. membrane. Receptors Bind intracellular receptors Bind cell surface receptors Signal As receptor complex, change Transduce signal via second gene expression directly messenger systems Examples Oestradiol-17β, progesterone, GnRH, FSH, LH testosterone 36 Questions? Clarifications? 37  Summary Intercellular chemical signals allow cells to communicate over varying distances (including autocrine, paracrine and endocrine/neuroendocrine) The hypothalamus and pituitary are major regulators of the endocrine system (including reproduction) Pituitary has two lobes that function in different ways and produce different hormone products Homeostasis of hormone levels is maintained using feedback loops (particularly negative feedback) Contrast steroid vs protein/peptide hormones (see table) 38  Can you answer these questions? 1. Can you define these terms? – Autocrine – Paracrine – Endocrine 2. Which organs act as the major regulators of the endocrine system? 3. How many lobes is the pituitary gland made up of? 4. What are the key differences between the two lobes? 5. What is the difference between a positive and negative feedback loop? 39  Can you answer these questions? 6. What are the four main steroid families called? 7. What are steroids derived from? 8. Where is pregnenolone produced? 9. How do steroids travel in the blood? 10. What are the major differences between steroid and peptide hormones? 40 Can you answer these questions? Draw the arrangement of neuroendocrine neurons on the outline of the hypothalamus and pituitary gland below. 41  Can you answer these questions? What kind of intercellular signalling is shown in each example below? Figures modified from: http://nchsbands.info/2017/endocrine-signalling.html 42  Reading for Lecture 2 Wheater’s Functional Histology (6th Edition): pages 337-350 Essential Reproduction (9th Edition): pages 110