Physiology II Hormones and Sex Differentiation PDF

Physiology II L. Segabinazzi 2024 DIESTRUS  Goals Physiology MM II - Reproduction Understand the fundamental differences betw...

Physiology II L. Segabinazzi 2024 DIESTRUS  Goals Physiology MM II - Reproduction Understand the fundamental differences between hormones, Remember the step by step of mitosis and meiosis Fetal sex differentiation – hormonal control and cell development Understand oogenesis and spermatogenesis Understand feedback and supraphysiological stimulation “downregulation” Endocrine control – hormonal feedbacks Ovulation, sperm maturation and capacitation, fertilization site and events, early embryo development Maternal recognition of pregnancy in different species Placentation and differences between species Fetal maturation Pregnancy development – endocrine control  Hormones Physiology MM II - Reproduction Chemical messengers Most hormones are: Secreted by an endocrine gland Carried by the bloodstream Affect other organs, glands, or tissues. Controls metabolic processes Signaling molecules produced in the body that regulate the activity of certain cells and organs  Classification of hormones Metabolize instomach Physiology MM II - Reproduction Stomach enzymatic degradation Chemical nature Amine hormones Protein/peptide Eicosanoids Steroid The amino acid-derived Larger proteins or Derived from Derived from hormones are relatively small/medium size peptides polyunsaturated cholesterol small molecules that (chain of amino acids) fatty acids from the Androgens are derived from the Much larger than steroids and cell membrane - Metabolized in amino acid tyrosine and amine hormones usually arachidonic the liver (first- tryptophan. Water-soluble – membrane acid (20-carbon) val pass)Cannot be Easily metabolized receptors Key mediators and orally gofthis Short peptides – Ex.: oxytocin Ex.: Estrogens, Name of amino acid- regulators of testosterone, derived ends in “-ine” Small proteins – Ex.: growth inflammation and progesterone Ex.: Melatonin, hormones immunity Epinephrine Glycoproteins – Ex.: FSH, LH Paracrine lipophilic to Smaller protein or Ex.: Prostaglandins available gooste peptide hormone theyant membrane produce by FSH hormone  ft Classification of hormones Physiology MM II - Reproduction Mechanism of action Faster xq of the second message Stevoid Bind to cell membrane receptors Bind to Just intracellular receptors Hydrophilic Lipophilic Transported in the free-form Found in the circulation in association with Hormones bind the cell membrane receptors (G- transport proteins (Ex.: albumin) protein), which induce the release of secondary Form hormone-receptor (H-R) complexes messengers. Biochemical function mediated by H-R complex Secondary messengers perform the biochemical function. H-R binds the DNA (hormone specific element) cAMP, Ca/Phosphatidylinositol, Protein Kinase / and activate mRNA transcription Phosphatase, cGMP Longer half-life (hours or days) Short Half-life (minutes) Ex.: Steroids Ex.: Amino acid derived and eicosanoids te cascade effect Slower xy have a longer of life then protein hornous Xg  Hormones Physiology MM II - Reproduction Hormone control: Negative or Positive feedback Most endocrine hormones are regulated by negative feedback loops. Negative feedback keeps the concentration of a hormone within a relatively narrow range and maintains homeostasis. Ex.: Testosterone is essential for spermatogenesis. However, excessive concentrations of testosterone cause negative feedback on the anterior pituitary for the release of LH, which will consequently reduce the activity of Leydig cells for the production of testosterone. Or increaseone will decrease Very few endocrine hormones are regulated by positive feedback loops. Positive feedback causes the concentration of a hormone to become increasingly higher. Ex.: Estradiol produced by the pre-ovulatory follicle causes positive feedback to the anterior pituitary for the release of LH. The LH will induce the ovulation of the pre-ovulatory follicle. in  B act El fl se Hormones Physiology MM II - Reproduction Supraphysiological stimulation bounces just protein Exceeding what is normally found in healthy individuals Hormone becomes ineffective after long-term use “Internalization” of hormone receptors Once the peptide/protein hormones are bound to their receptors on the appropriate target cells, they are internalized and degraded by the process of receptor-mediated endocytosis Ex.: Prolonged-release, high dose GnRH Used as a contraceptive in dogs and horses Physiologically, GnRH is responsible for follicular growth and ovulation when there is too much GnRH the receptors go inside and stop the process  Hormones in Reproduction Physiology MM II - Reproduction Source of production Hypothalamic-pituitary-gonadal axis Pineal gland: Melatonin Hypothalamus: GnRH anterior adenophy Pituitary Gland: FSH, LH, Prolactin, a Oxytocin release cute posteria adenophy Gonads: hypotonland Ovary: Follicles - Estradiol, Inhibin, Testosterone; Corpus luteum - Progesterone, Relaxin, Oxytocin Testis: Testosterone, Inhibin, Estradiol Uterus: Prostaglandin F2 alpha Placenta: Progesterone, Estradiol, hCG, eCG, Oxytocin, PGF2α  Hypothalamic-Pituitary Interrelationships Physiology MM II - Reproduction Hypothalamo-Pituitary Portal System ▪ A system of blood vessels in the microcirculation at the base of the brain, connecting the hypothalamus with the anterior pituitary. ▪ Axons of hypothalamic neurons extend to blood vessels of portal system ▪ Function: quickly transport and exchange hormones between the hypothalamus arcuate nucleus and anterior pituitary gland. ▪ Hormones: GnRH, GHRH (Growth hormone), CRH mum (corticotrophin), TRH (thyrotrophin) ▪ GnRH affects the anterior pituitary directly ▪ Hypothalamic centers (FEMALE*) ▪ Tonic – Regulates the release of frequent low amplitude tong ov GnRH pulses Both male and ferule ▪ Surge - Only in females – responsive to high levels of estradiol and release of high amplitude GnRH pulse regulatory Regulate by levels of Estrogens - Feedback  Early embryo development Physiology MM II - Reproduction Several mitotic divisions Early divisions occur without increase in cell mass “Cleavage” (or “Reduction Division”) Metabolic support provided by maternal secretions Zygotic protein synthesis begins at 2 to 16-cell stage depending on species (Totipotent cells) O Totipotent – capable to give rise to any tissue l Early embryo development Physiology MM II - Reproduction An important event during embryo life is the differentiation from the morula to the blastocyst stage. During the morula stage, the cells differentiate into two groups of cells InnerAtcell the (ICM) – stage massmorula polarized cells 0 in the “Blastocyst” that will form the embryo Trophoblast – will develop the chorion (placenta – external portion) In addition, the cells from the trophoblast the “pump” sodium into the intracelular space and because of the osmotic pressure, the embryo is filled with “water”, which forms the “Blastocele or Blastocoele”. 1 Blastocele will form the cavity that will surround the embryo. sac yolk  Embryology Physiology MM II - Reproduction Embryo starts as a mass of cells that eventually form layers and will differentiate into the embryo proper and placenta. had gastrulation place you 000 I  Embryology Physiology MM II - Reproduction Ectoderm **Mesoderm Endoderm ⚫Reproductive Tract ⚫Gonads (testes and Digestive system ⚫Caudal Vagina and ovaries) Respiratory system vestibule ⚫Uterus, cervix, Most glands ⚫Penis and clitoris cranial vagina ⚫Mammary glands ⚫Epididymis, ductus deferens Oogonia and ⚫Nervous system ⚫Hypothalamus ⚫Accessory sex Spertogenium glands ⚫Both lobes of the Pituitary ⚫Muscle ⚫Blood vessels ⚫Oral and nasal cavities ⚫Urinary system ⚫Skin, hair, nails, sweat glands ⚫Skeletal system Placental development Physiology MM II - Reproduction The trophoblast is the external cellsembryonic tissue Mhesoderm and gives rise to the placenta. Extraembryonic mesoderm and trophoblast constitute the (chorion). phase vom Expansion of the allantois forms the allantochorion. allantois phase  fetus Embryology Physiology MM II - Reproduction Embryo An organism in early stages of we development Generally, this embryo has not acquired an anatomical form that is Embryo readily recognizable in appearance as a member of a specific species Fetus Fetus Potential offspring within the uterus um that is generally recognizable as a member of a given species Marked by placentation development  Embryology: Sex differentiation 3 Genetic (chromosomal) sex Stages 1 Determined at fertilization XX (homogametic, homomorphic) or XY (heterogametic) in mammals ZZ (male) and ZW (female) in birds Gonadal sex weeka 2 Testis determining genes; SRY and SOX9 There are also ovary-determining genes (RSPO1, WNT) Phenotypic sex Phenotype describes the observed characteristics such as morphology, development, blood types, behavior - Tubular and external structures The expression of these characteristics depends on the genetics (genotype), but is also affected by the environment - AntiMüllerian Hormone, Testosterone, Dihydrotestosterone  Embryology: Sex differentiation Initially indistinguishable (about 6 weeks in large domestic animals) from endoderm Primordial germ cells migrate from outside the organism (yolk sac) into the organism through the hindgut to the undifferentiated gonad just within the dorsal body wall (also known as the genital ridge).  Embryology: Sex differentiation Physiology MM II - Reproduction Reproductive system develops at Mesonepfric = Wolffian ducts the same time as the renal system. Paramesonephric = Mullerian ducts Mulleria Iwolvin  Embryology: Sex differentiation Physiology MM II - Reproduction 1° Karyotype Female development XY - male is the default XX - female 2° Determination of physical sex organ characteristics relies on the presence of: “Sex-determining region Y” (SRY) on the Y chromosome and secretion of Testis Determining Factor (TDF) TDF is synthesized in the sex cord of males i Medullary sex cords differentiate into Sertoli cells; cortical sex cords degenerate Sex cords differentiate into seminiferous tubules and rete testis Male pre-Sertoli cells produce Anti Müllerian Then Anti-Müllerian hormone (AMH) Degeneration of paramesonephric duct _Mullevinducts Testosterone Development of the male ducts system Lastly, Dihydrotestosterone (T2 + 5α-Reductase = DHT) Development of: Penis, Scrotum, Accessory sex glands Embryology: Sex differentiation Physiology MM II - Reproduction i r r if  Embryology: Sex differentiation Physiology MM II - Reproduction ✔ Testis determining factor Testis development (Sertoli cells) ✔ AMH Development of the Leydig cells – is resumphric duct Testosterone – Male duct system Everything  Embryology: Sex differentiation Physiology MM II - Reproduction Absence of ✔ Testis determining factor ✔ AMH ✔ Testosterone  Embryology: Sex differentiation Physiology MM II - Reproduction Hypothalamus: Male vs. Female Female hypothalamus contains 2 functional areas for secretion of GnRH Tonic (arcuate ventromedial region; ARC) and Surge (preoptic area; POA) centers Hypothalamus is inherently female Testosterone during development “defeminizes” the brain Testosterone crosses blood-brain barrier and is converted to Estradiol Estradiol defeminizes hypothalamus, eliminating surge center ifs Fetal ovaries produce Estradiol, but this does not cross the blood-brain barrier because it is bound to alpha-fetoprotein (@FP)  Embryology: Sex differentiation Physiology MM II - Reproduction Fetal Maturation The fetal stage consists of rapid fetal growth and maturation of the organs that were produced during the embryonic stage. This is also the period of time when: Both gounds rule and female win te Gonads – retroperitoneal region (pelvic cavity) befo shuto In the male The testicles descend into the scrotum tintppen fr In the female Broad ligament development The ovaries migrate caudally due to fetal growth Metanephros enlarges and migrates cranially, below the suprarenal glands, which pushes the gonads laterally (6-9 weeks).  Embryology: Fetal maturation Physiology MM II - Reproduction ✔ Paramesonephric ducts (Mullerian ducts) Female – Oviduct/uterus E The broad ligament forms after the Mullerian ducts join together during development. The fusion of these ducts leads to the development of the female pelvic organs and cavity. ✔ Mesonephric ducts (Wolffian ducts) Male – epididymis/ductus deferens  Embryology: Fetal maturation Physiology MM II - Reproduction Ectoderm = Different embryological tissue origin Embryology: Sex differentiation Physiology MM II - Reproduction Freemartinnism Bovine (camelids, occasionally other species) Male and Female co-twins Early fusion of placental circulation gof this AntiMullerian Hormone (AMH) transferred from male to female Mediates regression of paramesonephric (Mullerian) ducts Vestigial development of vagina, cervix, uterus, uterine tubes Almost normal vulva and vestibulum Derived from urogenital sinus Ectoderm*  Testicular descent Physiology MM II - Reproduction CSL (cranial suspensory ligament) Two phases G (gubernaculum/caudal genital ligament) Inguinoscrotal phase Transabdominal phase Thickening of the gubernaculum Retroperitoneal position and increased abdominal Upper layer attached to the pressure (viscera) results in the diaphragm by the CSL dilation of the inguinal canal Testosterone degenerates the CSL Two layers of peritoneum Insulin-like hormone 3 (INSL3) Visceral vaginal tunic this docuthappen controls the gubernacular that Parietal vaginal tunic In case thickening and developing Reny et al., 2023 characteristics but is Present wall infertilediegte INSL3 is produced by Leydig cells spermatogonium Embryology: Sex differentiation Physiology MM II - Reproduction  Lorenzo Segabinazzi, DVM, MSc, PhD Ross University School of Veterinary Medicine THANK YOU [email protected] VETERINARY.ROSSU.EDU ©2021 Ross University School of Veterinary Medicine. 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