Cholecystokinin (CCK)
1) CCK Production a) Cholecystokinin It is produced by the enteroendocrine “I” cells which are located within the duodenum, jejunum and the ileum. Within the gastric pits we have the both chief cells and partial cells; these are the dominant cells within the stomach.
2) CCK Release 1) CCK will be release in response to an ↑ in the concentration of amino acid, fatty acid and HCl 3) Active CCK a) Active CCK is comprised of 8 amino acids. 4) Similar to Gastrin a) The last 5 amino acids and COOH group are exactly the same as those in gastrin. CCK 7th amino acid is different from gastrin. Similar in structure but with very different function.
5) CCK Physiological Function 1) ↑ in pancreatic enzyme secretion into the duodenum. Once the food starts to empty into the duodenum CCK will cause an increase in pancreatic enzyme secretion. 2) Involved in the contraction of the gallbladder.
3) Involved in ↑ pancreatic acinar cell mitosis 4) Stimulates intestinal cell mitosis 5) ↓ in gastric emptying to ensure we don’t overwhelm the duodenum with too much chyme
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! 6) Initiation of HCO! secretion from the pancreas, thus, HCl will be buffered
Secretin Family
Secretin
1) Production a) Secretin is secreted from enteroendocrine “S” cells of the small intestines 2) Actions a) Induces pancreatic enzymes secretion b) Inhibits gastrin secretion c) Inhibits gastric motility ! d) Stimulates additional HCO! secretion. 3) Secretin Stimulation 4) Acidic chyme entering the duodenum
Gastro-Inhibitory Peptide (GIP)
1) GIP Production a) Secreted by the enteroendocrine “K” cells which line the first half of the intestines. They are produced in response to either fat or glucose present within the small intestine 2) Actions a) GIP will b) GIP will c) GIP will inhibits glucagon by slowing down lipolysis. A ↓ lipolysis will ensure we preserve stored energy. d) GIP will activates lipoprotein lipase to take fats from the bloodstream and store it within cells
Vasoactive Intestinal Peptide (VIP)
1) VIP is a powerful vasodilator which is capable of
Somatostatin
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1) Produced a) Somatostatin is produced by the “Delta” cells of the pancreas 2) Somatostatin Actions a) Generally inhibitory 4 – 6 hours after meals b) ↓ in pancreatic activity (acinar and Islets) i) ↓ in insulin and glucagon production c) ↓ in acid production within the stomach
ANS Control of the Digestive System
Anticipation Phase
1) Acetylcholine is released and targets muscarinic receptors. The stimulus results from Vagus nerve signals. 2) Stimulates gastric acid secretion. 3) Stimulates salivary gland secretion
Digestion Phase
1) Tactile phase resulting from food in the gut. This results in a dramatic ↑ in enteroendocrine cell production
Intrinsic Nervous System
1) Myenteric Plexus a) Plexus innervates the outer two layers of the intestines and is responsible for peristalsis and churning of the intestines. The outer two layers contain circular muscle fibers and horizontal muscle fibers. 2) Submucosal Plexus a) Innervates the muscular mucosal layer (inner muscular layer) of the intestines and is responsible for assisting in intestinal folding b) Is capable of also causing contraction and vasodilation of the blood vessels surrounding the intestines which will allow for diversion of blood to other areas of the body or to increase absorption after we eat. 3) PNS: 4) SNS:
Digestion Overview
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Pancreatic Secretions
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Exocrine Pancreas: Main function of digestion via the acinar cells
1) Ductal Cells ! a) Produce HCO! to buffer the acidic chyme.
2) Acinar Cells a) Digestive enzymes are produced here
Endocrine Pancreas
~5% of the mass is represented by the Islets of Langerhans
1) α Cells a) Glucagon secretion 2) β Cells a) Insulin 3) ∆ Cells a) Somatostatin
Insulin Structure
A protein consisting of 2 polypeptides units
1) α Subunit a) ~ 21 amino acids long 2) β Subunit a) ~30 amino acids long 3) Synthesized initially from a single gene as pro-insulin
Synthesis and Secretion of Insulin
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Biphasic Release
1) Initial Release 2) Sustained Release
Factors Controlling the Release
1) Glucose Levels a) By a ↓ in plasma glucose levels b) An unidentified sensing mechanism exists. Probably an unidentified membrane receptor 2) Ingestion of proteins/fats a) Especially proteins 3) Autonomic Nervous System 4) Other Hormones
Degradation of Insulin at 3 Main Sites
1) Liver a) Has an ` ½ life of 5 minutes and the sulfide bonds are degraded by the enzyme
2) Kidneys a) Via glomular filtration 3) Pancreas a) Insulin protease via cleavage
Insulin Transmembrane Receptor
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1) General Characteristics a) α Subunit i) Attached to the cells outer membrane within the extracellular matrix on b) β Subunit i) Has a receptor tyrosine kinase which is located within the cell
Insulin Function within the Target Cell
1) Insulin binds to the α subunit 2) Activation of tyrosine kinase 3) Phosphorylation of cellular proteins 4) Activation of phosphotase 5) Transport of glucose across the membrane
Insulin/Glucose Pathway
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1
2
a b 4
3
i ii
6
8 5
7
Insulin/glucose Mechanism
1) Insulin binds to receptor alpha followed by activate of the tyrosine kinase residues
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2) Tyrosine-protein molecule is brought in à ATP to ADP. The tyrosine-protein is phosphorylated to activate the intracellular pathway. The phosphate comes from the ATP 3) Phosphorylates to activate the protein (insulin receptor substrate) a) IP3 kinase is activated to open GLUT 4 transporter which will allow glucose to enter the cell b) After glucose enters 2 pathways are possible i) Glucose storage after conversion to glycogen ii) Glycolysis à sugar à 2 pyruvates à CO2 and glucose 4) Activated phosphorylated protein will open other extracellular channels to allow other amino acids and electrolytes to enter the cell. These substrates will assist in protein formation 5) Activated phosphorylated protein à myogenic signals where transcription factors are activated followed by initiation of the RAS MAPK pathway. 6) Protein synthesis begins from raw materials which were brought into the cell. 7) Glycogen synthase phosphatase will convert inactive glycogen synthase into active glycogen synthase. 8) Active glycogen synthase will convert glucose into glycogen
Glucagon
1) Involved in glucose homeostasis 2) Functions to 3) 29 amino acids long 4) A member of the secretin family. Glucagon maintain a very similar structure to the secertin family but exhibits a very different function
[Glucagon] and [Glucose] Over Time
[Blood Glucose] mg/dL
[Glucagon] Time
***As serum [glucose] decrease, the [glucagon] will increase***
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Glucagon Secretion
1) Possibly a glucose sensory mechanism on the alpha cells 2) Secondary response a) An increase in protein release into the blood will cause a b) Amino acids c) Fats i) ↑ in free fatty acid circulation within the blood
Mechanism
1) Primary Actions a) Glycogenolysis
b) Gluconeogensis i) Creation of glucose or other energy sources from molecules other than glycogen 2) Secondary Actions a) Lipolysis i) Breakdown of fats into free fatty acids that will enter the bloodstream and be available as a source of energy. If the free fatty acids aren’t used as energy they will be restored within the cells.
Somatostatin
Somatostatin Production
1) Produced by
Somatostatin Functions
2) Pancreas a) 3) Calcitonin a) Calcitonin tones down serum Ca++ and ↑ one remodeling, thus, somatostatin will inhibit calcitonin 4) Pituitary Gland a) Inhibits HGH production 5) GI Hormones a) Inhibits digestion
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Diabetes Mellitus
Symptoms
1) 2) 3)
Types of Diabetes
1) Insulin Dependent -IDDM, Type I a) i) ↓ in β cells and a ↓ in insulin production b) High levels of auto antibodies against tissue c) Treatment i) Insulin 2) Non-insulin Dependent -NIDDM, Type II a) Insensitivity to insulin b) c) Almost non-existent in d) Subtypes based on receptor ability i) Pre-receptor resistance: Insulin is produced but not capable of activating the receptors (1) Insulin Antibodies (a) Insulin antibodies bind to insulin receptors on the cell surface and prevent cell activation, thus, no sugars, phosphates or magnesium will enter the cell. (2) Gene Mutation (a) Insulin is produced but is unable to bind to receptor which is shaped incorrectly
ii) Receptor Resistance: Receptor is unable to transmit a signal intracellularly, thus, its unable to active an intracellular pathway (1) Type A: Decreased insulin receptor number (a) ↓ in serum sugar and an ↑ in cell receptors à increased sensitivity (2) Type B: Receptors are blocked by antibodies (a) Insulin antibodies bind to insulin receptors on the cell surface and prevent cell activation, thus, no sugars, phosphates or magnesium will enter the cell. iii) Post-Receptor Resistance (1) Receptors are normal but there is an inability to express GLUT-4 proteins. Therefore, NO glucose is brought into the cell
Insulin Absence or Insulin Receptor Action
1) Inactive Glycogen Synthetase
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2) Increased Lipolysis/Decreased Cellular Glucose a) A ↑ in serum free fatty acids and glycerol secondary to the breakdown of triglycerides.
i) Metabolic Acidosis
(1) Ketones are excreted from the body in urine
(2) With the excretion of Na+
Treatment
1) Decreased tissue response to insulin increases the need for insulin a) Decreased Insulin demand i) Obtained via weight reduction with exercise b) Oral Treatment i) Sulfonaureas
2) Diet a) b) c) 3) Exercise a) b)
4) Hypoglycemic Agents a) Oral Treatments i) Sulfonureas ii) Meglitnides iii) Biguanides iv) DPP-4
***Side Note***Diabetes Implications of Cardiovascular Disease and Polyneuropathy
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Adrenal Medulla
The Catecholamine
Adrenal Glands
1) Cortex a) Steroidgenic Cell Types b) Secretes 2) Medulla a) Neural Crest Tissue- i) Derived from neural tissue which was originally ectoderm b) Adrenal medulla + Sympathetic nervous system = c) Secretes catecholamines i) Epinephrine (~80%) and Norepinephrine (~20%)
***Note*** The sympathetic nervous system mainly secretes
Autonomic Nervous System
1) ANS neurons innervate viscera vessels, skin, heart, GI tract, skeletal muscle, kidneys, bronchial passageways and potentially the pancreas and liver Endocrinology Spring 2013 Page 81
a) Vasomotor Neurons b) Secretory Neurons
Parasympathetic Nervous System (Craniosacral Division)
1) Nerve origination is off of the brainstem and off of S1, S2 and S3 (pelvic splanchnic nerves)
Sympathetic Nervous System (Thoracodorsal Division)
1) Nerves originate off of T1 – L2 2) Celiac, Superior mesentery and Inferior mesentery ganglion
Preganglionic Neurons
1) Postganglionic - PSNS 2) Postganlionic – SNS
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Adrenal Medulla
Autonomic Neurotransmitters
1) Cholinergic Fibers release ACH a) ACH is released from all preganglionic ANS fibers. This includes both parasympathetic and sympathetic fibers.
Pre-ganglionic Post-ganglionic
b) ACH is released from all postganglionic parasympathetic fibers. The effects are short lived and local secondary to the presence of acetylcholinesterase. 2) ACH Post-synaptic Receptor Sites a) The effects on the target organ dependent on the receptor on that organ i) Nicotinic Receptors (1) Receptor for ACH on the post-ganglionic synapse (dendrites + cell body). (2) Results (a) They will cause firing of all the parasympathetic and sympathetic postganglionic nerve fibers. ii) Muscarinic Receptors (1) Receptor for ACH on all the parasympathetic target organs and some sympathetic target organs. (2) Results (a) The results are variable; can cause excitation or inhibition. It just depends on the organ
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Catecholamine Synthesis
1) Phenylalanine is the precursor for tyrosine
Parkinson ’s Disease
DOPA will cross the blood brain barrier but dopamine will not.
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Adenorecptors
1) Alpha Receptors (α)
a) �! i) PRIMARILY STIMULATORY ii) Postsynaptic receptor iii) iv) PKC activating
b) �! i) PRIMARILY INHIBITORY ii) Presynaptic receptors iii) Will bind to catecholamine’s (1) Bind epi/norepi on the presynaptic receptor to prevent future release of epi/norepi (2) (3) Receptors also found on the cholinergic neurons (secrete ACH). (4) (5) Also present in vascular smooth muscle to induce contraction; activate G Inhib protein 2) Beta Receptors (β)
a) �! i) Cardiac muscle – on both the atria and ventricles (1) (2)
***Side Note***Beta Blockers will
ii) Adipose tissue (1)
b) �! i) Location (1) Vascular (2) Bronchiolar (3) Uterus smooth muscle (4) Skeletal muscle (5) Liver ii) Will cause
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Sympathetic NS Negative Feedback Mechanism
�!
Multiple Mechanisms for Signal Transduction
�! �! �! �!
Physiological Actions: Primarily to maintain homeostasis. Any decrease in blood pressure, plasma glucose or O2 levels will increase activity to reverse these processes
1) Cardiovascular System a) Heart i) b) Vascular Smooth Muscle
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i) ↑ in vasoconstriction of ii) Coronary, bronchial and skeletal muscle vasodilation 2) Respiratory System a) Bronchial smooth muscle relaxation 3) Metabolism a) CHO i) ↑in serum glucose levels via hepatic gluconeogenesis via ii) Promotes glycogen secretion via iii) Inhibition of insulin from pancreas via b) Fat i) Promote lipolysis via β1 receptors 4) Secondary Functions a) Adrenal Cortex i) Induces the formation of PMNT
↑ in cortisol à ↑ in PMNT production à ↑ the release of norepi à ↑ the release of epi
b) Renin-Angiotension-Aldosterone System
***NOTE ***
c) Pancreas
i) β! receptors à ↑ glucagon secretion ii) α! à ↓ insulin production
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Epinephrine/Norepinephrine
Liver Adipose Tissue Kidneys Pancreas Respiratory Arteries Heart B! B! α! ↑ Renin, ↑ BP B! B! α! B!
Hormones of the Adrenal Cortex
1) Zona Glomerulosa
2) Zona Fasciculata
3) Zona Reticularis
Control of the Different Sections
1) Glucocorticoids a) Produced in the zona fasciculate and regulated by i) Hypothalamus
ii) Anterior Pituitary
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b) Primary Action i) Regulates carbohydrate metabolism and stimulates glycogen synthesis
c) Diurnal Release i) Release affected by (1) Fever (2) Psychosis (3) Stress (4) Hypoglycemia (5)
Physiological Action
1) Most every cell in the body has receptors for cortisol, but there are a large number of receptors on a) b) c)
The Nuclear Receptor:
A DNA binding protein
Activation of DNA Binding Protein
Occurs through a confirmation change
Intermediary Metabolism
1) Increase in synthesis of gluconeogenic enzymes
2) Catabolic reactions
3) Amino acid transport to the liver
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4) Glucose uptake by tissues
Synergistic Actions Synergistic action to other hormones
1) Required for proper SNS function 2) Helps maintain temp 3) Synergistic to EPI and glucagon
Anti-inflammatory Response: Stages of Inflammation
1)
2)
***Glucocorticoids ***
Aldosterone Produced by the zona glomerulosa of the adrenal cortex
Angiotensinogen
Renin
Angiotensin I
ACE
Angiotensin II
Location for Renin production
Renin’s primary role
Renin’s affect on the adrenal cortex
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Aldosterone’s affect on the kidney’s
Target Cells: Collecting duct
Various hypotheses on how aldosterone works on these cells
Blood Volume and Blood Pressure Regulation
Aldosterone Functions
Renin/Aldosterone System
1) The Juxtaglomerular Apparatus
a) The JG cells
b) The Macula Densa 2) The Secretion of Renin
a) A decrease in extracellular volume
b) Stimulation of the SNS
c) Decrease firing of the stretch receptors in afferent arteriole
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Angiotensin II Functions A very powerful vasoconstrictor
1) Aldosterone
2) Smooth muscle
3) Neurons of brain
4) Ganglionic transmission
5) Norepi synthesis
6) Thirst
Overall Function
1) Angio II type I receptor
2) Angio I type II receptor
Regulation of H20/Na+ Balance
1) Atrial Natriuretic Peptide release
a) Functions i)
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ii)
iii)
iv)
v)
b) General Stimulus for release
c) Overall Result
2) Aldosterone
3) ADH a) Produced
b) Function
i) Baroreceptor
(1) Carotid and aortic arch
(2) Low pressure in the left atria
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(3) High pressure in the aortic/carotid arteries
ii) Hypothalamic Osmoreceptors
iii) Angiotensin II
iv) Norepinephrine
c) Actions of ADH i) V1 receptors
ii) V2 receptors
iii) Renal
iv) Vascular smooth muscle
v) Liver
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Reproductive Endocrinology General Genetics 1. Gametes Ova 23 chromosomes Sperm 23 chromosomes
Sex Differentiation Gonads The sex of an individual is generally determined by hormones produced at the testis or ovary.
The gonads regulate: Functional development of reproductive tract Adult sex characteristics Adult male and female brain Gonads are divided into two regions: Cortical Region – outer region, Medullary Region – inner region,
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SRYGene Determines the If the SRY gene is present the embryo will TDF (Testis Determining Factor) Transcription factor that
Interstitial cell produces testosterone. Testosterone is important in male reproductive tract development 5 α reductase converts
Sustentacular cells – produce
SRY Proteins are turned on about 5-10 days after fertilization (before implantation) Testicle formation begins about the 7th week of gestation. Ovary formation occurs about 14 week 'of gestation
Embryonic Development of the Human Reproductive System 1. Wolfian Ducts (SRY gene present) a) Sustentacular Cells - MIF
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b) Interstitial Cells - Testosterone
Dihydrotestosterone –
Gynecomastia -
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2. Mullerian Duct (SRY gene absent) so no MIF, male Wolfian ducts will deteriorate
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Hormonal Effects on Brain Structure Human Male: continuous secretion of GNRH (hypothalamus), FSH, LH (ant. pituitary)
Human Female: cyclical production of GNRH (hypothalamus), FSH, LH (ant. pituitary) Factors to turn on switch for puberty
Control of gonadotropins by: hypothalamus preoptic area Effect of Testosterone on hypothalamus –during neonatal period the hypothalamus is sensitized providing continuous secretion of GNRH for male reproduction.
Testosterone effect on preoptic Area of Hypothalamus – increase in size and number of the cells in the preoptic nucleus.
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Effects of Testosterone and Estrogen on Male Reproductive Development
Maturation and Endocrine Development of the Female Brain
E2 regulates masculinization of the male brain. Why not the female brain?
Estradiol levels are low during the prenatal desensitization period. FEBP – Fetoneonatal estrogen binding protein
Male Reproductive Anatomy Sustentacular Cells (Sertoli Cells)
Involved in Sperm Maturation FSH effects on Sustentacular cells- produce
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The blood testes barrier –
Inhibin Production - hormone produced by testis for negative feedback
slows down sperm production
Interstitial cells –
The Male Reproductive Hormonal Feedback Mechanism
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Functions of Testosterone on the Male reproductive System Prostate Gland – 1/3 seminal volume, Seminal Vesicles – 60% of seminal volume,
Epididymus – continuation of sperm maturation Anabolic Effects – increase growth of muscle mass tissue increase hair growth, deepening of voice, increase mascularity.
Synthetic Androgens Negative Feedback Mechanism – give exogenous testosterone will decrease GNRH, LH, FSH production – DHT 2 ½ more times more potent than testosterone need 5 α dehydrogenase. Testosterone Receptor Binding. Secondary Sex Characteristics – Side Effects
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Reproductive Endocrinology of the Female Ovarian Function Produce gametes Make hormones
Tissue Types Epithelial Tissue: provides support like Mesenchymal Tissue: produces estrogen like
Oogenesis The Primordial Follicle (At Birth) – 2 million at birth, 400,000 at puberty (menarc = 1st cycle, menopause = end of cycle)
How many eggs ovulated in lifetime?
Stages of Oocyte Development Quaternary Stage: Cell Differentiation Thecal Cells – develop from Granulosa Cells – proliferate as oocyte enlarges directly surround oocyte (species specific)
Thecal Vascularization – thecal cells produce angiogenin (increase in blood flow) – corpus hemoragicum – after delivery – stays with ovary (luteal cyst) corpus luteal cyst
Development of-the Antrum – steroids growth factors & electrolytes 100-200 times higher here than other parts of the body
The Mature Graafian Follicle
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The Antrum The Anatomy of the Human Ovary
Day 1-5 develop primary follicles Day 6-10 primary follicle (initially 25) (atresia deteriorate) function is to produce significant amount of estrogen secondary follicle – estrogen in high levels Day 13 Graafian follicle – spike in LH – follicle ruptures, thecal cells stay behind, granulosa cells continue with egg Day 14 ovulation Day 15-17 corpus hemorrhagicum – outer thecal cells with blood center Day 18-28 corpus luteum Day 29-31 corpus albicans – scar tissue
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Ovulation occurs follicular wall thins luteinizing hormone and prostaglandins stimulate granulosa cells stimulate plasminogen activator converts plasminogen to plasmin along with that collagenase (proteolytic enzyme) helps to break down the follicular wall to allow ovulation to occur.
Characteristics of the Secondary --> Graafian Follicle increase LH receptors on thecal cells increase vascularity in thecal cells increase inhibin to decrease FSH production
Hormonal Input and Follicular Development Circulating levels of FSH are constant throughout the cycle. Prior to differentiation of follicular cells into thecal and granulosa cells little hormones are produced.
The Synthesis of Estrogen
Thecal is analogous to interstitial cells of Leydig Granulosa – early in cycle (analogous Sertoli) have only FSH receptors – LH receptors develop later from increased estrogen levels so they can bind to LH in the second ½ cycle.
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Ovulation Both FSH and LH are needed for ovulation to occur LH peak is noted prior to ovulation due to a gradual increase in estrogen An increase in E2 causes an increase in number of GnRH receptors on the hypothalamus Estrogen levels decrease after menopause and there are E2 receptors on osteoblasts. Bone density decrease (osteoporosis) The follicle that develops the fastest begins secreting estrogen at a rapid rate and cause a negative feedback to the hypothalamus causing FSH production decrease making other follicles.
Estrodiol – β-17 –
Estriol –
Estrone –
Corpus Luteum Lifecycle Pregnant Female: placenta produces hCG, which binds to LH receptors. The progesterone from the corpus luteum maintains the endometrium for implantation and vascularity of the endometrium
Fertilization occurs where?
Syncytial trophoblast –
Non-Pregnant Female: A decrease in progesterone levels ant about 14 days post ovulation begin the process of luteolysis (maintains corpus luteum).
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Hormones of the Menstrual Cycle Estrogen is dominant hormone at
Progesterone is dominant hormone at
Follicular Phase –
During this phase plasma level of FSH is relatively high to cause the development of follicles to produce estrogen, whereas progesterone, LH and estradiol are low.
Functions of FSH causes an increase in LH receptors on granulosa cells causes follicular growth increases the activity of aromatase which converts test to E2
Follicular Phase (Second Half) - Now a decrease in FSH is noted, while an increase in estrogen from follicular production, and an increase in LH, inhibin, and E2 are noted. Estradiol and inhibin produced by the dominant follicle cause a decrease in FSH this increases the testosterone/estradiol ratio in the non-dominant follicle. More testosterone= atresia (death of that follicle) An increase in estradiol = increase in GnRH = peak in LH = ovulation
Luteal Phase - Second half of the entire cycle - During this phase of the cycle an increase in progesterone, and estradiol are noted.
A decrease in LH and FSH are seen during this time.
Contraceptive Pill – prevents ovulation by
Progesterone has a negative feedback on the release of GNRH. Progesterone tells the hypothalamus to stop producing GNRH. Decrease estrogen production because no follicles are being produced – less able to support egg plantation. Progesterone inhibits sperm penetration
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Fertilization awareness Basil body temperature 0.5-1.6 degree increase Fertile, vaginal mucus –
Cervical changes in position and texture. Fertile
Non-Fertile –
Vulva (external female genitalia)
Hormones of the menstrual cycle Proliferative phase is first half – dominant hormones are FSH and estrogen (anterior pituitary gland) Leutial phase – corpus Luteum and LH hormone Secretory phase – progesterone
Cycles of the Endometrial Lining Two Phases Follicular Phase- due to production of estradiol from the developing follicles the endometrium gradually thickens.
Luteal Phase- during the second half of the cycle the endometrium maintains thickness and begins to
Luteolysis
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Pregnancy and the Corpus Luteum Human Chorionic Gonadotropin hCG from the embryonic tissues increases the production of progesterone within the first two weeks after ovulation. hCG is very similar in structure to LH and FSH, so it binds to LH receptors on the corpus luteum, thus maintaining it until
Then the corpus luteum regresses. Also a critical time in fetal development
The corpus luteum also produces Relaxin in response to hCG. This hormone serves several functions: relaxes –
relaxes -
RU486 – morning after pill, high doses of estrogen and progesterone shut down production of LH, these high levels decrease GnRH, LH, FSH producton. Continued thinning of the endometrium lining, aids in stopping implantation – abortifacient
64 cells morula – blastocyst – syncicial trophoblast
Pregnancy The zygote enters the uterus at
It implants approx.
At this time the "blastula" has two separate cell layers. Cytotrophoblast: the inner cell mass that makes up the components of the embryo.
Syncytial Trophoblast: makes up the extra-embryonic membranes that produce steroid and protein hormones. (hCG – placental hormone smilar to LH in structure) becomes completely imbedded into the membranes. Endocrinology Spring 2013 Page 113
The Hormone of the Placenta hCG - the placenta produces hCG at approx. 14 days post conception - These levels continue to increase to at about 9 weeks post conception then slowly decline to about near the end of the second trimester.
Function: maintains the luteal phase to increase and maintain progesterone by the corpus luteum and the production of relaxin.
Progesterone - produced by the corpus luteum up to six weeks post conception and then by the placenta from 6 weeks until the end of the pregnancy. The placenta produces the enzymes required to produce progesterone from cholesterol.
Function: Maintain uterine vascularity and thickness, maintains uterine relaxation prior to delivery. Inhibits FSH and LH production during pregnancy Initiates the development and growth of breast tissue Estrogen – estriol is the major estrogen produced during pregnancy in the corpus luteum.
Sensitivity of the hormones – fetal steroids are commonly sulfated which protects the fetus from high exogenous steroid levels
α feto proteins – glycoproteins synthesized by the yoke sac in the liver and excreted into the amniotic fluid. Binds to estrogens to decrease estrogen availability.
Increased levels can indicate
Decrease in α feto proteins can indicates
D.O.C. – deoxycorticosterone – mineral corticoid causes salt and water retention (20 times increase) provides extra fluid for volume expansion and development of the body, especially blood volume.
LH during pregnancy increased levels of progesterone causes decreased levels of LH secretion increased levels of estrogen causes a decrease in LH synthesis
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Breast-Feeding This mechanism suppresses
This mechanism stimulates the release of endorphins,
Lactation The Mammary Glands - These modified sweat glands contain a large blood supply. Epithelial cells- cells that produce the milk, during lactation their metabolic machinery works of a high rate. Secretory cells – Prolactin – Ampulla contain epithelial cells oxytocin causes constriction
Myoepithelial cells- muscle cells that serve to contract to squeeze milk into the ductules
Breast Tissue Development Puberty - Estradiol is involved in growth and development of the ducts. While progesterone is involved in the development of the alveoli During Pregnancy - PRL major hormone in the production of milk - E2 and Progesterone are involved in the maturation of the ducts and epithelial cells. An increase in suckling causes an increase in PRL. PRL levels are high at parturition but drop off significantly about three days after birth. The initiation of breast-feeding maintains high levels of PRL Milk: Let-Down (Ejection) Reflex - This is a neural reflex. Stimulation of the nipple or a stimulatory thought process (hearing a baby crying) initiates release of oxytocin from the posterior pituitary gland to cause contraction of the Myoepithelial cells and smooth muscle cells of the ampulla. These contractions cause milk: to be released from the breast. Human placental lactogen produced by syncitial trophoblast similar to GH and Prolactin in structure and functions overlap seen in womens plasma after (10 days) conception as placenta grows HPL levels increase is anabolic, lipolytic, and antagonistic to
Helps to increase breast development in mom Parturition – baby birth
Fetal ACTH increases cortisol synthesis Causes shift from more progesterone production to estrogen production Ratio change increases uterine contracting through increase in prostaglandin production
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