1. Endocrine Glands & Hormones Learning Objectives: To understand what the reproductive endocrine glands and hormones are. To understand the characteristics and functions of these hormones. To understand how the concentrations of these hormones in the blood are controlled. BY ABDUL SAMIK DEPARTMENT OF VETERINARY REPRODUCTION, FACULTY OF VETERINARY MEDICINE, UNAIR

2. Endocrine Glands of Reproduction Body Diagram of Endocrine Glands

3. The reproductive process in mammals is governed by the central nervous system. Information emaniting from a variety of external cues (eg. Visual, auditory, tactile, olfactory) is fed into the centralnervous system and converges on the Hypothalamus. The information is proessed, amplified, transduced to a humoral signal and transmitted to the anterior pituitary gland where it is further amplified and transmitted via the gonadotrophic hormones to gonads. The latter respond in many ways, one of which is by the secretion of sex hormones. These, in turn, act on a host of target tissues including the brain and pituitary gland. This form a vastly complex network of information transfer, a network that permits amplification, propagation and integration of signals throughout the body. Organization of control system governing reproduction

4. The hypothalamus is located in the brain, at the base of the optic chiasm. The hypothalamus consists of nervous tissue lying inferior to the two lobes of the thalamus. The pituitary gland, or hypophysis, is found at the base of the brain below the hypothalamus and the two structures are connected via the infundibulum, or pituitary stalk, which carries both axons and blood vessels. It secretes hormones that stimulate or suppress the release of hormones in the pituitary gland, in addition to controlling water balance, sleep, temperature, appetite, and blood pressure Hypothalamus Brain Diagram of Endocrine Glands

5. The hypothalamic boundary is limitted frontally by the optic chiasma, caudally by the mamillary bodies and dorsally by the thalamus. The hypothalamus surrounds the fluid-filled third ventricle. It is made up of various types of structural elements including cell bodies of hypothalamic neurons with their axons and terminals. Axons and terminals of other neurons with cell bodies lying outside the hypothalamus and axons passing through from extrahypothalamic neurons. The cell bodies of the hypothalamic nuclei send axonal projections to one of four general regions : 1.Other areas of the brain 2.Other hypothalamic nuclei 3.The median eminence 4.The posterior lobe of the pituitary gland Anatomical organization of the Hypothalamo-hypophyseal axis

6. The median eminence The median eminence comprises the base of the hypothalamus and is continuous with the pituitary stalk. It contains few, if any, nerve cell bodies, but consists of axons and terminals of both hypothalamic and extrahypothalamic neurons, glial cells and specialized ependymal cells called tanacytes. The latter cells line the third ventricle and are of potential importance in the transfer of information from the cerebrospinal fluid to the pituitary gland. The neural structures of the median eminence contains a capillary plexus connected with the hypothalamo-pituitary portal system.

7. The pituitary gland or hypophysis is sometimes called the "master" gland of the endocrine system, because it controls the functions of the other endocrine glands. The pituitary gland is located at the base of the brain. The gland is attached to the hypothalumus (a part of the brain that affects the pituitary gland) by nerve fibers. The pituitary gland itself consists of three sections: the anterior lobe (adenohypophysis) the intermediate lobe the posterior lobe (neurohypophysis) The pituitary gland:

8. Hypothalamus - Pituitary interrelationships

9. The anterior pituitary is derived from oral epithelium from the roof of the mouth cavity, which migrates upwards towards the neural tube It sits in the sella turcica which is a depression of the sphenoid bone at the base of the skull and lies behind the sphenoid sinus. The anterior lobe of the pituitary is further subdivided into the pars distalis, pars intermedia and pars tuberalis The anterior pituitary makes up 75% of the total weight of the pituitary. The pars distalis forms the major part of the gland. The pars tuberalis surrounds the infundibular stem like a cuff and extends upwards to lie beneath a portion of the median eminence The anterior pituitary contains no nerve fibers and terminals and so is not in direct neuronal contact with the hypothalamus. The anterior pituitary connected to the brain by a vascular connection, the hypothalamo-hypophyseal portal system. The anterior pituitary gland consist of many different cell types classified on the basis of their size, shape and histological staining characteristics.

10. Somatotrophs secrete growth hormone (GH), are distributed laterally and make up 50% of hormone secreting cells. Thyrotrophs secrete thyrotropin (TSH), are concentrated laterally and make up 10% of cells. Gonadotrophs secrete luteinizing hormone (LH) and follicle stimulating hormone (FSH), are randomly distributed and make up 10% of cells. Corticotrophs secrete adrenocorticotrophic hormone (ACTH), b- lipotrophin, a -melanocyte stimulating hormone and b-endorphin, are found in the median portion and make up 15-20% of cells. Lactotrophs secrete prolactin, are randomly distributed and make up 25% of cells. The number of these cells increases in response to increased oestrogen in pregnancy and lactation. The posterior pituitary develops as an extension of the hypothalamus itself. The infundibulum is formed from the neuroectoderm of the floor of the third ventricle and develops to form the posterior pituitary. The median eminance is also formed from neuroectoderm.

11. anterior lobe: growth hormone prolactin - to stimulate milk production after giving birth ACTH (adrenocorticotropic hormone) - to stimulate the adrenal glands TSH (thyroid-stimulating hormone) - to stimulate the thyroid gland FSH (follicle-stimulating hormone) - to stimulate the ovaries and testes LH (luteinizing hormone) - to stimulate the ovaries or testes intermediate lobe: melanocyte-stimulating hormone - to control skin pigmentation posterior lobe: ADH (antidiuretic hormone) - to increase absorption of water into the blood by the kidneys oxytocin - to contract the uterus during childbirth and stimulate milk production

12. HYPOTHALAMO-PITUITARY AXIS STRUCTURE AND DEVELOPMENT Blood Flow The pituitary receives blood supply from paired superior and inferior hypophyseal arteries which originate from the internal carotid arteries. The superior hypophyseal arteries enter the primary capillary plexus of the median eminance close to the nerve endings of the neuroendocrine cells of the hypothalamus. From here, blood flows down the portal veins to the sinusoidal vessels of the anterior pituitary This provides a direct vascular link between the hypothalamus and anterior pituitary secretory cells. There is also thought to be a reverse flow of peptides along the infundibulum back to the brain which may provide a rapid feedback mechanism. Venous drainage is into the dural sinuses surrounding the pituitary gland. Blood supply to the posterior pituitary is from the inferior hypophyseal arteries directly from the systemic blood flow.

13. Nerve Pathways The hypothalamus is innervated from many areas of the brain, including the limbic system, cerebral cortex, thalamus and other areas. This is due to its important role in regulating many vital functions such as maintenance of body temperature, appetite, emotions, pain, intellect etc.as well as control of endocrine functions. The hypothalamus contains two groups of nuclei with neuroendocrine functions. These are the paired supraoptic and paraventricular nuclei and the hypothalamic-hypophyseotropic nuclei. The posterior pituitary contains the termination of axons from the supraoptic and paraventricular nuclei, which abut onto capillaries. These cells produce vasopressin and oxytocin, which are stored in and secreted from the posterior pituitary gland. The newly synthesised hormones are packaged with the protein neurophysin and move down the nerve fibres by fast axonal transport. They then move by exocytosis into the efferent blood vessels of the posterior pituitary. Some of the axons of the supraoptic nuclei terminate in the upper infundibulum so some vasopressin may still be produced following loss of the posterior pituitary.

14. The anatomy of the Neurohypophysis The posterior pituitary is derived from the forebrain during development and is composed predominantly of neural tissue. The posterior pituitary lies below the hypothalamus, with which it forms a structural and functional unit: the neurohypophysis. The neurohypophysis consists of three parts: 1.the supraoptic and paraventricular nucleii of the hypothalamus (containing the cell bodies of the magnocellular, neurosecretory neurones that synthesize and secrete VP and OT); 2.the supraoptico-hypophyseal tract (which includes the axons of these neurones); 3.and the posterior pituitary (where the axons terminate on capillaries of the inferior hypophyseal artery). The supraoptic nucleus (SON) is situated along the proximal part of the optic tract. It consists of the cell bodies of discrete vasopressinergic and oxytotic magnocellular neurons projecting to the posterior pituitary along the supraoptico-hypophyseal tract. The paraventricular nucleus (PVN) also contains discrete vasopressinergic and oxytotic magnocellular neurons projecting to the posterior pituitary along the supraoptico-hypophyseal tract. The PVN contains additional, smaller parvicellular neurons projecting to the median eminence and additional extra-hypothalamic areas including forebrain, brain stem, and spinal cord. Some of these parvicellular neurons are vasopressinergic.

15. A group of those projecting via the median eminence co-secrete VP and corticotrophin releasing hormone (CRH), and terminate in the hypophyseal-portal bed of the anterior pituitary. These neurons have a role in the regulation of adrenocorticotrophin (ACTH) release. The posterior pituitary receives an arterial blood supply from the inferior hypophyseal artery and the artery of the trabecula (a branch of the superior hypohyseal artery), derivatives of the internal carotid artery and its branches. The SON and PVN receive an arterial supply from the suprahypophyseal, anterior communicating, anterior cerebral, posterior communicating and posterior cerebral arteries, all derived from the circle of Willis. Venous drainage of the neurohyphysis is via the dural, cavernous and inferior petrosal sinuses. Schematic representation of the anatomy of the neurohypophysis, and it's major afferent and efferent connections

16. Anatomy of the Pineal Gland The pineal gland is a small organ shaped like a pine cone (hence its name). It is located on the midline, attached to the posterior end of the roof of the third ventricle in the brain. The pineal varies in size among species; in humans it is roughly 1 cm in length, whereas in dogs it is only about 1 mm long. To observe the pineal, reflect the cerebral hemispheres laterally and look for a small grayish bump in front of the cerebellum. Histologically, the pineal is composed of "pinealocytes" and glial cells.

17. How does the retina transmit information about light-dark exposure to the pineal gland? Light exposure to the retina is first relayed to the suprachiasmatic nucleus of the hypothalamus, an area of the brain well known to coordinate biological clock signals. Fibers from the hypothalamus descend to the spinal cord and ultimately project to the superior cervical ganglia, from which post- ganglionic neurons ascend back to the pineal gland. Thus, the pineal is similar to the adrenal medulla in the sense that it transduces signals from the sympathetic nervous system into a hormonal signal.adrenal medulla

18. Structure: A flattened ovoid shape, 3 - 5 cm in diameter The outer (periphery) ovary is the cortex and is fibrotic. It contains: –Germ cells, or ova, which are contained in follicles –Corpora lutea - produce oestrogens and progesterones –Corpora albicantes - degenerate The stroma is the body of the ovary, containing: –Fine collagen fibres –Scattered bundles of smooth muscle cells –Some stromal cells may contain lipid droplets The mature ovary will contain many follicle of different sizes and development. OVARY

19. Diagramatic Representation of the Ovary:

21. TESTIS Macrostructure: Paired, ovoid structures Capsule: –External: tunica vaginalis –Internal: tunica albuginea Gland is divided into intercommunicating, testicular lobules by fibrous septa –produce androgen-binding globulin: this is in response to FSHFSH similar to plasma sex hormone-binding globulin maintains high androgen levels in the testis and seminal fluid –produce inhibininhibin inhibits FSH secretion –produce seminiferous tubule fluid Between the seminiferous tubules are the interstitial LEYDIG CELLS where androgens are produced. androgens –these cells only have LH receptors, which stimulate steroidogenesisLH –Also produce small amounts of oxytocin, endorphins, angiotensins, and prostaglandins oxytocin Microstructure: Each testicular lobule contains seminiferous lobules - site of spermatogenesis The basement membrane of the seminiferous tubules is lined with SERTOLI CELLS. These: produce mullerian-inhibiting substance convert androgens to oestrogen act as a supportive cell for the developing germ cells (sperm) form a blood-testis barrier

23. A chemical substance secreted by an endocrine gland or group of endocrine cells that acts to control or regulate specific physiological processes, including growth, metabolism, and reproduction. Most hormones are secreted by endocrine cells in one part of the body and then transported by the blood to their target site of action in another part, though some hormones act only in the region in which they are secreted. Chemical types of hormones: Peptide - Few - Several amino acids Protein - Long chains of amino acids Glycoprotein - Protein hormone with carbohydrate molecules DEFINITION OF HORMONE

24. HORMONE ACTION PROTEIN HORMONESTEROID HORMONE

25. GlandHormone Chemical ClassPrincipal Functions Ovary Graafian Follicle Estrogens (Estradiol) SteroidMating behavoir, Secondary sex characteristics, Maintenance of female duct system, Mammary growth Inhibin (Folliculostatin)Protein Regulates release of FSH from anterior pituitary Corpus LuteumProgestins (Progesterone) Steroid Maintenance of pregnancy, Mammary growth & secretion Relaxin PolypeptideExpansion of pelvis Dilation of cervix

26. Testis Leydig CellsAndrogens (Testosterone) SteroidMale mating behavior, Spermatocytogenesis, Maintenance of male duct system & accessory glands Sertoli CellsInhibin ProteinRegulates release of FSH Adrenal CortexGlucocorticoids (Cortisol) SteroidInduction of partruition by fetus Milk synthesis Stress response PlacentaHuman Chorionic Gonadotropin (HCG) GlycoproteinLH-like - Involved with establishment of pregnancy in human. Support and maintain CL Endometrial Cups Mare Equine Chorionic Gonadotropin (eCG) Old name - Pregnant Mare Serum Gonadotropin (PMSG) GlycoproteinFSH-like- some LH activity Immunological protection of foal during pregnancy Formation of accessory CL in mare Estrogens/Progestins SteroidsRegulate placental bloodflow Maintenance of pregnancy Relaxin ProteinRelaxation/dialation of cervix for parturition Placenal Lactogen GlycoproteinStimulates mammary growth & milk secretion

27. Uterine Endometrium Graafian Follicles Seminal Vesicles Prostaglandin F2a (PGF2a)LipidRegression of CL,Stimulate myometrial contractions Ovulation Sperm transport LiverInsulin-like Growth Factors IGF-I & IGF-II Protein Stimulates steroidogenesis, Stimulates mammary growth and fetal development Pineal GlandMelatonin Biogenic amine Control of seasonal reproduction in Mare & Ewe Regulate hair growth Posterior PituitaryOxytocin OctapeptideStimulate myometrial contractions for sperm transport, parturition & milk ejection

28. Anterior Pituitary Follicle Stimulating Hormone (FSH) - Follicotropin GlycoproteinStimulate follicle growth Stimulate estrogen production Spermiogenesis in male Luteinizing Hormone (LH) - Luteotropin GlycoproteinStimulate ovulation Support CL formation, and progesterone secretion Stimulate testosterone synthesis by leydig cells of testis Prolactin ProteinStimulate milk synthesis Regulate metabolism for milk synthesis Effects Maternal Behavior Adrenalcorticotropic Hormone (ACTH) ProteinRelease of corticosteroids & glucocorticoids from adrenal cortex to initiate parturition

29. HypothalamusGonadotropic Releasing Hormone (GnRH) DecapeptideStimulates release of FSH and LH from anterior pituitary Dopamine Biogenic AmineInhibits release of prolactin Corticotropic Releasing Hormone (CRH) PeptideStimulates ACTH release Growth Hormone- Releasing Hormone (GRH) PeptideStimulates release of growth hormone OxytocinOctapeptideProduced by the hypothalamus, released at the posterior pituitary.