Endocrinology and Homeostasis

Endocrinology

• Endocrinology is a bioregulatory field that studies the homeostatic principles within bodies, essentially bioregulation

Homeostasis

• "Set point range" refers to a level at which the body tries to stay
• High triglycerides in the blood can increase the risk of heart disease, stroke, and pancreatitis
• Doctors check blood levels, and anything that is "outside of the range" can provide information about a person's health

Why Important?

• Bioregulation of homeostasis within blood is prevalent in modern science and medicine
• A hematocrit measures the percentage of red blood cells in a body
• Around 18% hematocrit level is considered low and is one of the first indicators of leukemia
• A 60% hematocrit level would be too high, possibly indicative of liver issues that cause an overproduction of blood cells
• Blood tests also test hormone levels
• Overall, blood tests measure the presence of bioregulatory molecules
• Triglycerides are a type of fat found in the bloodstream.

Stress Response

• When exposed to a stressor from the environment, it triggers the release of stress bioregulators
• The hypothalamus, with its direct connection to the pituitary, ultimately controls this release

Cortisol

• Cortisol is considered a stress hormone released by the adrenal gland
• High cortisol levels indicate hyperphagia

Types of Stress Responses

• Acute stress response is quick hyperphagia that can have benefits
• Chronic stress response is the body trying to get through the stress, so it will "eat" sources within the body for energy to survive
• All of the food gets burned up, then the fat , and then the proteins(muscle & skeleton) = not good
• Giving food immediately to people who have gone through months or years of starvation causes harmful effects
• It is best to first provide fluids and introduce a small amount of protein with fat until the body has acclimated

History of Endocrinology

• Formal study of endocrinology began in the 19th century
• Pioneers like Hippocrates & Bordeu developed findings that contributed to the advancement of bioregulatory science

Hippocrates: 460 B.C - 370 BC

• Wrote "Disease of the Scythes"
• Noticed cyclic processes (like menstruation in females & genital development in males) happened around the same time in, leading him to believe that there must be some system within
• Hypo-orchidism is the underdevelopment of genitalia/secondary sexual characteristics

Theophile de Bordeu: 1722-1776

• In the same era modern endocrinology began
• Wrote "Chronique maladies", writing about chronic illnesses
• Wrote of emanations into the blood that he believed were chemical properties produced in the body that govern the function of organ tissues/systems

Research Methods

• Radio Aminoacyl: Labels hormones/biochemicals
• Lyso-assay measures levels in the blood by being Enzyme-linked
• Melatonin regulates the circadian clock, so ultimately governed by the adrenal cortex

Health Crisis

• Exposure may increases the risk of developing chronic and/or fatal illnesses

The top 3 contributors

• Cancer
• Endocrine Disruption
• Diabetes

Endocrine Disruption

• Linked to the alteration of mammary glands, for example fracking may be linked
• Biggest concern = plastics, that release synthetic fibers that alter endocrine functions
• These synthetic fibers are on clothes, drinking bottles, and so much more
• Mimic endocrine/bioregulatory molecules & can block receptors

Bald Eagle

• In the 60s, they were endangered due to exposure to chemicals that caused changes in the physiology
• Production of calcium carbonate in their eggs got interfered with
• In 1970s, the clean air & water act and the endangered species list began
• DDT was banned and bald eagle numbers went back up

The Basics

• The endocrine system, nervous system, and immune system are constantly in direct communication with one another

What Cells Do

• The basic structural and functional unit of all living organisms
• Building blocks that make up tissues, organs, and systems in the body
• Make and use energy to make things and to make things happen (like proteins, enzymes, other bioregulators, communication/signaling, etc)
• Doctors check blood levels and if anything is "outside of the range" it can provide information about a person's health

Hormones

• Hormones act on target cells
• Bioregulators tell cells to make things

Levels of Chemical Bioregulation

• First messenger system is followed by a second messenger system

Evolution the History of an Idea

• Zeitgeist = "time spirit"
• Key questions ask what the scientific climate was at the time and who the important figures where, not just Darwin

Three Important Terms

• The fact of change
• The course of change
• The mechanism of change (the how)

Carolus Linnaeus: (1707-1778):

• Changed his name after being knighted to Carl von Linne lmao in 1758
• Developed a hierarchical system to classifying organisms and a naming system for species (domain, kingdom, phylum, class, order, genus, & species
• He is the "Father of taxonomy" or "Father of botany"

Leading Naturalists: natural philosophers

• Rev. John Ray (1627-1705):
  • "Wisdom of God Manifested in the Works of the Creation" (1691).
• William Paley (1743-1805):
  • Archdeacon of Carlise and a Natural Theology expert
  • "Evidences of Existence of and the Attributes of the Deity Collected from the Appearances of Nature"
• Louis Agassiz (1807-1873):
  • He was Swiss
  • Curator of Comparative Anatomy at Harvard University
  • Established the museum to house the manifestations of the Creator, believing species DO NOT CHANGE
• Jean-Baptiste de Lamarck (1744-1829):
  • French best known for early theories of evolution
  • Suggested idea of inheritance of acquired characteristics, where organisms could pass on traits they acquired during their lifetime
  • Proposed the fact, course, & mechanism of change and the "Philosophie Zoologique" (1809)
• Alfred Russel Wallace (1823-1913):
  • Member of the lower-class in England
  • An explorer on the brig Helen ship, collected specimens as they traveled extensively through the Amazon basin & Indonesia
  • In 1858, arrived to the Spice Islands (Moluccas Islands)
  • They are part of the Malay archipelago with lots of biodiversity
  • Wrote letter Thomas Malthus ("An Essay on the Principle of Population.."), wondering what limited population growth with big factors war, conflict, natural diseases!
  • This inspired him to think about what makes some people able to survive these things and not others, acquiring his ideas on carrying capacity from Malthus
• Charles Lyell (1797-1875):
  • Wrote the first ideas that suggest plate tectonics
  • "Father of modern geology"
  • Presented evidence for an Old Earth with his 3 volume set that set sail with Darwin, inspired many of his ideas

Charles Darwin (1809-1882)

• Father was a doctor, mother was a part of the Wedgwood pottery family
• Attended the University of Edinburg to be a doctor, but he was very squeamish & could no longer do it
• Went to Cambridge to get his “divinity degree" to become a priest
• "Collected beetles & drank beer at the pub" with Darwin's friends
• Became a 'naturalist' for the HMS Beagle w/ Fitzroy, leaving in 1831
• During the Voyage of the Beagle (1831-1836) discovered the Galapagos Islands and Medium ground finch
• At his home Down House in Kent, he artificially selected/bred pigeons and studied barnacles, particularly their reproduction
• Gets a letter from Wallace in 1858, presenting his similar findings

Natural Selection

• Differential success in the reproduction of the phenotype out of an organism's interactions with its environment has 4 tenants:
• Variation exists among individuals of a population with regards to a trait
• There's a difference in fitness among individuals; there is a correlation between the trait and the ability to reproduce
• This variation is heritable
• If all of these factors are in place, the frequency of traits in subsequent generations will be predictably different from that of previous generations.
• Natural selection is NOT survival of the fittest

Natural Selection & Fitness

• Brad Pitt Lion:
• "Charismatic megafauna" - people love large animals
• Scar was more 'fit' than Mufasa
• Darker mane indicates more testosterone therefore higher fitness
• Mart Gross & Bluegill Sunfish:
  • Gross researched mating tactics in bluegill sunfish with sexual dimorphism, since females are are smaller and darker
  • Females produce eggs & males spawn; they protect the nest together
• Their sexual dimorphism suggests that sexual selection is playing a large since the differences are distinct
• Existence of “sneakers”; smaller & darker fish that are actually males that sweep in to the nests, release their sperm into the eggs, & sneaks out, allows them to get some portion of their genes into the next generation
• These sneaky look like females & have the chemical signature of females (smells like them; pheromones)
• Survival of the fittest is not the best way to describe natural selection, because the biggest, stronger, or fastest does not necessarily mean the most ‘fit' to survive in these conditions
• Dung Beetles:
  • Energy is the most important thing for organisms, that comes from food

Monsanto's Roundup

• “Better Living through Chemistry" with Glyphosate
• Genetically modifies the genome of plants for them to be resistant to herbicides and pesticides
• Allows farmers to spray the entire crop without killing desired plants
• The Roundup Problem:
• The emergence of roundup-resistant weeds, pointing out how natural selection makes this approach no good

Antibiotic Resistance

• Scariest pathogen for doctors right now are Fungal infections, and the extreme rise in fungal infections is scary because of resistance occurring

AIDS Pandemic

• This virus mutates very quickly
• Originally a wild-type of AIDS virus
• Doctors was trying everything & most treatments would work for just a little bit, however the "Pharmaceutical cocktails" were metabolized by the body because they are not natural, leading to liver damage, making AIDS used to be a death sentence
• A young airman was diagnosed with HIV & went to a German doctor that gave him a 'drug cocktail' of like 20 different drugs, however virus always came back because of mutations, which caused doctor came back with a lower viral count & lower mutant forms, with almost all of the virus being wild-type type that is easier to treat
• Removal of the chemical environment allows the wild-type to outcompete other forms & to survive, resulting in 'shock'-removal treatment

Important Concepts

• Adaptation represents differential survival and reproduction of individuals in species populations over time, plus any morphological, physiological, developmental, or behavioral character that enhances survival and reproductive success of an organism
• Fitness measures the contribution of a given genotype to the next generation relative to that of other genotypes
• Evolution is the process of change in populations over time, including directional change or cumulative change in characteristics generation to generation

Comparative Vertebrate Evolution

• Life began 500 to 700 million years ago
• Evolutionarily conserved = “go back to the beginning", where many bioregulation aspects have to be evolutionarily conserved
• For example, in vertebrates, in the way we develop as a zygote
• Closest relatives to vertebrates are acorn worms
• First endoskeleton = cartilage
• Sleeper shark:
  • Deep ocean in the Arctic with 'super cooled' body temp is just slightly above freezing
  • Lives for 100s of years old
• Agnata is jawless fish
• Complex life cycle of tadpoles indicates the bioregulatory dependence/important, where bioregulatory feedback drives this life cycle in response to changing environments
• We are traced back to reptile-like mammals, one specific group which is indicative of the evolutionary conservation

Vertebrate Evolution

• Vertebrates hold a lot of evolutionary and bioregulatory mechanisms
• We exist because of the Therapsid group that survived the KT extinction event 65 mya
• We came from the group that resided in the trees during the day & underground at night, making them better suited to survive after KT since they were able to stay underground

Bioregulation

• Specific information in large quantities, so categorical organization is a useful and important tool
• Bioregulators: biochemicals that regulate cellular/bodily processes, organized by nervous system level, tissue/organ level, and/or external environment level

Nervous System/Neurons

• Chemical communication
• Neurotransmitters: secreted by neurons into the synaptic cleft (example: dopamine; evolved for motivation)
• Neuromodulators: secreted by neurons into the synaptic cleft with regulation that modulates sensitivity of the postsynaptic cell
• Endorphins impacts how much one lets stimulate the postsynaptic neuron
• Neurohormones: secreted by neurons into the bloodstream with Oxytocin stimulates contractions during childbirth
• These neurocrines are located at the tissue/organ level, secreting hormones by specialized cells into the bloodstream like Insulin

Cytocrines

• Secreted by specialized cells into the extracellular fluid but not the bloodstream, acting locally rather than systematically
• Norepinephrine acts as a neurotransmitter but can also have local hormone effects like increasing heart rate & causing vasoconstriction, which raises blood pressure
• Subcategories of Cytocrines:
• Autocrines - Affect the same cell that secreted them.
• Example: Some growth factors that stimulate their own production.
• Paracrines - Affect nearby cells.
  • Neurotransmitters or immune signaling molecules are an example
• Intracrines – Act inside the cell that produces them without being secreted.
  • cAMP and IP3 (intracellular messengers), which are involved in signaling pathways

Note

• Pituitary gland is highly regionalized: different parts of the pituitary contain different cell types that secrete distinct hormones. Cytocrines & Their Functions:

1. Growth factors: Stimulate cell growth & division
2. Regulatory cytocrines: Control cell activity
3. Tissue-inducing factors: Influence differentiation and development
4. Secretagogues: Enhance secretion of substances.
5. Tissue-inducing inhibitors: Prevent certain tissue responses External Environment Level:

• Semiochemicals are complex chemicals secreted into the surrounding environment
• Pheromones: only affect individuals of the same species, or intraspecific
• Primer pheromone: initiates some series of physiological events
• Male pheromones preparing females for reproduction are an example
• Signal pheromone: initiates an immediate behavioral response
• Allelomones: interspecific where Allomones impacts only the emitter benefits from the effect and Kairomones where the recipient species benefits, these are often used as an “attracticide"

Organization of Bioregulatory Systems

• W.B. Cannon was a pioneer in bioregulatory science & study of homeostasis
• Developed the first definition of homeostasis in 1929
• Homeostasis: “Balanced physiological systems operating in the organism to maintain a dynamic equilibrium (range)."
• Blood tests measure a homeostatic set point range
• high urea levels can be indicative of a possible liver issue
• Set point range & measuring those levels is very complicated be so many factors can cause deviations (like high cortisol levels in the morning)

Homeostatic Reflex Model

• The Hypothalamus acts as the receiver-kind of like a computer chip/control machine, translating input so the other parts of the body can 'understand'
• Homeostatic Hot Response has Vasodilation, where arterioles dilate so more blood enters the skin capillaries and heat is lost, and Sweating with Sudorific glands secrete to remove the heat
• Homeostatic Response has Vasoconstriction, Shiverying Piloerection, Curiling up, as well as Pilorelaxation (hairs flatten) and Stretching out (by opening up larger surface area)
• Integrating bioregulators and functions is an evolutionary marvel centered at the brain in the Hypothalamus & Pituitary
• The endocrine controls nervous system & somatic and the
• The liver manages itself but also takes orders from the boss (AKA hypothalamus)
• Endocrine organs: Everything that uses regulation
• Chromaffin cells: Make up adrenal gland

Methods in Bioregulatory Research

• Dependent variable: What the investigator measures
• Independent variable: What the investigator varies during the experiment
• Controlled variable: Variables held constant during an experiment, helping to eliminate the possibility that other factors are affecting the outcome of the investigation
• Level of treatment should also be looked at, determining the appropriate values used for the independent variable with Replication to replicate ones experiment to determine if results are consistent

Power Analysis

• Ensure that the correct power of statistical analysis is being employed
• Use a certain sample size of the right ethics, like measuring chronic stress in 10 turtles rather than 100
• Examples: Secretion by specialized cells and Insulin levels

Types of Methods

• Competitive Assay: measure the concentration of hormones, metabolites, or other small biomolecules
• Radioimmunoassay (RIA): uses radioactively labeled hormones to quantify hormone concentrations in samples
• Enzyme-linked Immunosorbent Assay (ELISA): non-radioactive alternative to RIA for measuring hormone levels in biological samples
• A detection enzyme is linked to the antibody or hormone and a substrate is added, producing a color change

Bioregulator Transport & Vehicles

• Vehicle: Solution to transport bioregulator into body where some bioregulators are water/lipid-soluble.
• When working w/ dihydrotestosterone (DHT) in tube, microperforations in the tubing are problematic because lipophilic compounds may leak out, leading to inconsistent dosing
• Bioregulatory Strategies:
  • Sustained vs Acute Delivery: injecting large amount of testosterone ineffective b/c body rapidly metabolizes & clears it Smaller doses are better
• Osmotic Pumps: release a precise amount of bioregulator uses Osmotic gradient to gradual push into delivery chamber
• Sham-Operated Procedures: control for surgery effects and hormone release with thyroidectomy turtles to reduce risk.

Dose-Response Relationships

• Relationship between concentration and physiological response
• Highly variable: depending on a lot of factors like species, time of exposure, or hormone
• Threshold Dose: minimum effective dose
• Sub-Threshold Response: no physiological change occurs
• Plateau Phase: No increase in response after plateau.
• Optimal Dose: Lowest effective dose
• Species Specific and Time Specific Responses
• Species metabolism & their receptors
• Hormesis curve

The Crash Course - Live of a Bioregulartor:

• Bioregulator: an external stimulus that triggers the endocrine to then synthesis and trigger Release
• Release Bioregulator Fates: secretion ,transport, and metabolic
• Protein transports are needed to reach their destination in soluble bonds
• Regulation goes back to Bioregulator to tell the body to stop producing by feedback.
• Hormesis, Ocam and Steroid Receptor (S)
• What happens and where did they change their metabolic ways.

What Does Scientific reasoning look Like?

• Occam's Razor, "a waring" where the Principle of Parsimony states when multiple explanations exist, the simplest one should be considered first,
• Use in hypothesis is a important test tool and is the the results we would expect to occur .
• Morgan's Canon , animals neuroscience always use the least invasive, and help prevent other problems with results.

What We Study About Bioregulators

1. Synthesis- Where and how is it made?
2. Metabolism- How is it modified used or broken down?
3. Actions- What does it do in the body?
4. Vestigal-Some Bioregulators exist but have lost their first part or function in the body.
5. Amino Acids,

What WE Study About Bioregulators

• Classic Bioregulators has everything that we need in life
• Amino Acids-

1. Includes neurotransmitters and neuromodulators

• Example: Tyrosine, an amino acid that acts a Bioregulator
  • Precursor to T3, T4
• Lipid (require protein
• Steroids are an intracellular
• Leukotrienes are fatty acids or lipids.

Types of Steroid Hormones:

• Major function are regulation of protein

• Glucocorticoid: Extracts from no carb by the body use of glucose if there isn't enought then lips for energy, the body will begin to break down.

• adaptation for survival

• Anti-imflammatory

• Major hormone: aldosterone Function: Regulation in the kidney

• Muscle and communication function. High blood pressure

Sex Steroids Gonadal Steroids

• Gonadal steriods like the rest, are a class of hormones produced in the testes and ovaries.
• They regualte sexual devlopment and reproductive function, the charestercirsitcs.
• Androgens:
• Primary =tesosterone in vertebrates, this stumates the development of secondary sexual characteristics in males.
• Inccrease mussel mass
• Voice deepening
• Strength leading to sexual que.
• Aggressive behavior -Sermateogenesis Sperm count
• Prosuction:
• O varies that estrogen by thesis
• Immune suppression and risks
• High testersoterne levels that are suporessed Esterogens function.
• Strucrual of esteriodoil biological activity Uterine and conification ( uterine lining.
• Regulating the sexual characteristics.
• Stimulates vascularization = embryonic effecters
• FSH production stimualte production.
• Progesterone is known as prego harmones supports preg. and the sustian state.

Thyroid Hormones:

• thyroid hormones are unlike other hormones.
• Primary Thyroids are:
• T3: metablice demadn of the body.
• More activated than T4
• Hydrophobic (protein production):
• Thyroid Function
• Controls energy/ storage
• Imapct developement and function in early roles
• Treatments of Thyroid
• Hypertyroism treatment:
• Receptros
• Production issues
• Supplement treatemnets
• Endocrine Diptors
• Chemicals are Interfeer with Endocrine function:

Action Function.

• Receptros/
• Biosythesis degration
• Hormoeonal is a development of hormonal functions
• Exagtion: interal folding Flint Michigan:
• Heavy metal in bodies are neurodevelpmental
• Exposure to hormeoal
• Impairmence

Chemical and Endocrine disruption

Chemicals enter and cause long-range disruption to the body. DDT is a Mid 20th century pesticide used to stop insects, and organic op pesticides. Aimed ta reducing malaria They also have regulatory system Rachel Carson's silent sprint: to declining populations

• Accumilation; chemicals and tissue

DDT chemicals

• The eagles the Chemicals were not there due to breakdown to carbonbads, and extipatred it in 1829 reintduced a couple years later.
• Gilette: he studied lous to the reproduction for american allies. Tesoserone was in the level of the water, and lakes also tested, Lake APPOP:
• The place company did a dumo in the lake and disruption, and some malforimiaton.
• Most have been a healthy, normal amount except those in AROK areas.
• Plastes begin in early day and are never broke down.