Hormones, Reproduction, Immunity, and Renal Function

Posted on Dec 15, 2024 in Biology

Reproductive Hormones and Functions

Major Classes of Reproductive Hormones:

Androgens – steroids
Estrogens – steroids
Gonadotropins – protein hormones
Progesterones – steroids

Androgens (Masculinizing Actions)

Key Androgens: Testosterone, DHEA (dehydroepiandrosterone), Androstenedione, DHT (dihydrotestosterone).

Testosterone

Produced by Leydig cells in testes, ovaries, adrenal gland, and placenta.
Stimulates testes and penis function.
Induces male secondary sex characteristics.
Stimulates protein anabolism, bone growth, and cessation of bone growth.
Required for sex drive and may enhance aggressive behavior.
Stimulates erythropoietin secretion by kidneys.

DHEA and Androstenedione

DHEA = dehydroepiandrosterone.
Formed in the adrenal gland.
Initiate puberty in ovaries.
Promote production of pubic and underarm hair.
Essential for sexual desire and satisfaction.
Not sufficient for testes reproductive functioning if testosterone is not produced.

Dihydrotestosterone (DHT)

Derived from testosterone.
Converted in target tissues by 5-α-reductase.
More potent than testosterone, with 5 times greater affinity for androgen receptors.
Stimulates embryological formation of penis and testicles.
Found mainly in prostate and hair follicles in adults.

Estrogens (Key for Anatomically Female Reproduction, Present in Everyone)

Key Estrogens: Estradiol, Estrone, Estriol.

Estradiol

Often used synonymously with estrogen.
Produced by the ovary, placenta, testes, adrenal gland, and fat cells.
Functions: growth hormone for breasts, uterus, ovaries; important for ovarian cycling and puberty; prevents apoptosis of sperm; important for bone development.

Estrone

Produced by ovaries and fat tissue.
Present in very low levels in the body.
Main estrogen in postmenopausal people.
High levels are very damaging (cancer, nausea, headache, hypertension, erectile dysfunction, etc.).

Estriol

Very low levels in everyone except during pregnancy.
High levels during pregnancy.
Fetus adrenal gland produces DHEA, which is then converted to estriol in the placenta.

Gonadotropins (Stimulates Production of Androgens and Estrogens)

Produced in the Anterior Pituitary, Stimulated by gonadotropin-releasing hormone (GnRH) in the Hypothalamus: Luteinizing Hormone (LH) & Follicle-Stimulating Hormone (FSH).

LH – Luteinizing hormone
FSH – follicle stimulating hormone
Present in everyone.
Gonadotropins produced by the anterior pituitary.
Stimulated by Gonadotropin releasing hormone (GnRH) from the hypothalamus.

LH and FSH Effects on Testes

LH stimulates Leydig cells in testes to produce testosterone.
FSH stimulates Sertoli cells in testes to produce sperm and inhibin.
Testosterone and inhibin provide negative feedback to the anterior pituitary.

LH and FSH in Ovaries

LH triggers ovulation and maturation of the corpus luteum.
FSH is essential for egg maturation.

Progesterones

Made by ovaries, placenta, and adrenal glands. Levels change throughout the ovarian cycle. Those without ovaries have continuous moderate levels.

Essential for maintaining pregnancy.
Lowers BP.
Provides significant protection against heart disease.
Offers protection against osteoporosis.
Necessary for balancing many other hormones and nutrients in the body.

Ovarian Cycling

Egg released halfway through, bleeding is day 1. The ovary allows a follicle to mature, and then pressure in the fluid-filled sac pushes the egg out of the ovary to the fallopian tube.

Follicular Phase

Egg maturation, granulosa cells, and theca cells appear around the oocyte, and those cells respond to LH and FSH.

Selection of the Dominant Follicle

Feedback loop acting on all follicles. As follicles get larger, their granulosa cells produce more inhibin and estrogen. Once one follicle reaches a critical size, it will produce enough inhibin to significantly decrease FSH production. This will slow development in other follicles. This large follicle is then the “dominant” follicle. This dominant follicle will continue to produce enough estrogen to promote its own development.

Ovulation

Estrogen levels in the blood will continue to increase as it is produced by the dominant follicle. Eventually, it reaches a critical level and then begins to provide positive feedback on GnRh and LH secretion. This leads to a rapid increase in LH levels known as the “LH surge.” This stimulates ovulation.

Luteal Phase

Remaining granulosa and theca cells remain to become the corpus luteum. The corpus luteum will degenerate within 2 weeks unless stimulated by pregnancy. The corpus luteum will produce inhibin, progesterone, and estrogen to inhibit LH and FSH production.

Corpus Luteum

Temporary Endocrine Structure.
Produces: Progesterone, Estradiol, Inhibin.
Functions to maintain the endometrium in preparation for implantation.

Pregnancy – Fertilization

Fertilization occurs in the Fallopian Tube.
First stages of development occur while the zygote travels along the fallopian tube to the uterus.
The egg relies on its own energy stores and diffusion at this point.
A person is not considered pregnant during this phase; pregnancy begins at implantation.
Many fertilized eggs do not implant.

Implantation

Implantation occurs ~ 9 days after ovulation.
The embryo must stimulate further production of progesterone so the uterine lining isn’t shed.
Once implanted, the embryo begins producing Human Chorionic Gonadotropin (HCG).

HCG

Keeps the corpus luteum alive so it will continue to pump out progesterone.
A likely cause of “morning sickness” (nausea and vomiting experienced by many people).
Hormone detected in home pregnancy tests.
Once large enough, the placenta takes over progesterone production, so HCG levels drop.

Placenta

Highly specialized structure for gas and nutrient exchange between parent and infant.
Parent and infant blood never touch.
Infant blood vessels bathed in parents’ blood.
Lots of surface area for diffusion.
Produces Progesterone.

Parturition (Birth)

Remember: Pregnancy starts and ends with a metabolic crisis. The second MC: The parent can no longer supply enough energy for the baby’s developing brain. If gestation goes on too long, the infant will start to metabolize its own fat reserves. CRH also stimulates the release of oxytocin from the posterior pituitary, which causes the release of oxytocin. Oxytocin stimulates the contraction of smooth muscles of the uterus, which initiates the third positive feedback loop. These positive feedback loops end only with the birth of the baby. After the baby is born, contractions continue for a few minutes as hormone levels drop. This allows for the delivery of the placenta.

Three (+) FB Loops of Birth

Infant under metabolic stress, releases ACTH from the Pituitary. ACTH stimulates Cortisol Release from the Adrenal Gland. Cortisol stimulates corticotropin-releasing hormone from the placenta (CRH). CRH creates a positive feedback loop in the infant by causing further release of ACTH from the pituitary.
CRH also causes the release of ACTH and cortisol in the parent, which causes further CRH release in the placenta.
Oxytocin stimulates uterine contraction, which causes the fetus’ head to stretch the cervix, which stimulates further release of oxytocin.

Lactation

Stimulated by suckling on nipple mechanoreceptors, neural input from the hypothalamus. Ant. pit (PRF to prolactin), oxytocin (post. pit.).

Renal System

RS: kidneys, ureter, bladder, urethra.

Kidneys

The left kidney lies superior to the right kidney.
The superior surface is capped by the adrenal gland.
Position is maintained by: overlying peritoneum, contact with adjacent visceral organs, supporting connective tissues.

Renal Function

Maintain water and ion balance in the body – nephrons (temp, lubrication, waste, blood volume, and flow).
Produce erythropoietin.
Produce 1,25-(OH)2Dihydroxycholecalciferol (active hormonal form of vitamin D) in response to PTH, promotes absorption of Ca2+ from the Intestine.

Nephrons

Nephrons are the functional units of the kidney.
Located in the cortex and medulla of the kidney.
Drain into the renal pelvis.
About 1 million nephrons.
Each nephron consists of a renal corpuscle, which contains the glomerulus (which is a tuft of capillaries) and a renal tubule.
The tubule forms a cup shape around the glomerulus called the glomerular capsule (Bowman’s capsule).

Juxtamedullary Nephrons

Long loop of Henle.
Involved in the concentration of urine.
Found at the border between the cortex and medulla.
About 15% of all nephrons are in this category.

Cortical Nephrons

Most nephrons are in this category.
Short loop of Henle.

3 components of urine formation: glomerular filtration, tubular secretion, tubular reabsorption.

Filtration

Forces for: glomerular cap. BP. Against: fluid pressure in Bowman’s space, osmotic force due to protein in plasma. Dilated AA, then more GFR.

Reabsorption

Occurs in nephrons. Most of the filtrate is reabsorbed by the renal tubule cells and returns to the blood through the peritubular capillaries.

Tubular Reabsorption

Molecules leave the filtrate and pass through the tubular epithelium to enter the blood vessel.

Paracellular Transport

Occurs between cells (even though they have tight junctions) and is seen mainly with ions.

Transcellular Transport

Occurs when substances pass through cells. Transport can be active (requires ATP) or passive (no ATP).

Tubular Secretion

Substances such as hydrogen ions, potassium, and organic anions move from the peritubular capillaries into the tubular lumen.

Division of Tubule Labor

Majority of reabsorption – Proximal Tubule and Loop of Henle.
Very little volume remaining in the distal tubule and collecting duct.
Fine-tuning – Distal tubule and collecting duct.

Urine Formation

Proximal Tubule

Reabsorption: HCO3, H2O, K+, NaCl, Nutrients.
Secretion: H+, NH3.

Descending Limb of Loop of Henle

Water leaves the filtrate passively through osmosis.

ALoH (thin segment)

NaCl (salt) leaves the filtrate passively through diffusion; Urea enters the filtrate passively through diffusion; the membrane is impermeable to water.

ALoH (thick segment)

NaCl (salt) leaves the filtrate through active transport; the membrane is impermeable to water.

Distal Tubule

Reabsorption: HCO3, H2O, NaCl, Ca++.
Secretion: H+, K+.

Collecting Duct

Water and some urea leave the filtrate. Urine leaves the nephron and enters the ureter, has highly acidic and highly concentrated filtrate.

Overall

Retains nutrients, water, NaCl, bases. Flushes urea, acids, toxins.

Vasopressin

Aka antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin.
Peptide hormone, released by the posterior pituitary.
Increases water reabsorption in nephrons.
Constricts arterioles, raising blood pressure.

Aldosterone

Produced in the renal cortex.
Steroid hormone.
Stimulates Na+ reabsorption by the distal convoluted tubule and the cortical collecting ducts.
Induces synthesis of Na+ ion channels and pumps in the cortical collecting duct.

Regulating Na+ Levels

Angiotensin II stimulates aldosterone secretion.
Angiotensin II levels are controlled by renin through the renin-angiotensin system.
Renin is released by juxtaglomerular cells.

Immune System

Innate and Adaptive.

Innate

Unspecific response to some general molecular property of an invader.
Usually responds to a molecule (carbohydrate or lipid) on the cell wall.
Three main pathways:
- Preventative – Body System Defenses (skin, hair, mucous, antimicrobial agents, stomach acid).
- Cellular: phagocytes and chemical release.
- Chemical: Interferons, complement cascade.

Cells

White Blood Cells (aka leukocytes). Generally larger than red blood cells. Can leave circulation and enter tissues. Many types, many functions.

Macrophages

A type of leukocyte.
Found strategically placed in nearly all tissues.
Functions: Phagocytosis, Secrete Toxins, Process and present antigens, Secrete Cytokines.

Dendritic Cells

Type of leukocyte.
Found in nearly all tissues.
Highly motile.
Specialized as microglia in the CNS.
Functions: Phagocytosis & Process and present antigens.

Neutrophils

A type of Leukocyte.
Produced in Bone Marrow.
Phagocyte.
Release vasodilators and chemotaxins (attract immune cells).
Other types of leukocytes can also be attracted depending on the pathogen type.

Phagocytosis

Intracellular killing of microbes.

Toll-like Receptors

A type of pattern recognition receptor (PRR).
Allow the body to recognize general molecular features of pathogens known as pathogen-associated molecular patterns (PAMPs).
Usually receptors bound to the plasma membrane of immune system cells like macrophages and dendritic cells.

Mast Cells

Type of leukocyte.
In connective tissues.
Not usually in blood.
Many cytosolic vesicles.
Functions: Release histamine and other chemicals involved in inflammation.

Cytokines

Protein messengers produced and released by immune cells.
“The neurotransmitter of the immune system.”
Usually act as an autocrine or paracrine substance but can circulate in the body as a hormone.
Form a highly complex network of communication leading to signaling cascades.

Inflammation

Response to injury or infection.
Identify and destroy pathogens.
Prepare for repair.
Steps:

Pathogen introduced into the body.
Cytokines and other chemical mediators cause vasodilation and recruit neutrophils.
Diapedesis and Phagocytosis by Neutrophils (or other leukocytes).
Vasoconstriction as neutrophils (or other leukocytes) clear the infection.

Vasodilation

Increased delivery of messenger proteins and leukocytes.
Increased permeability to protein ensures that the plasma proteins participating in inflammation can enter the interstitial fluid surrounding the pathogen.
Causes localized redness, swelling, heat.

Post-inflammation

Tissue repair.
Proliferation of Fibroblasts (connective tissue stem cell).
Blood vessel proliferation – angiogenesis.

Interferons

Specialized Cytokines:

Type I Interferon

Released by many types of cells in response to viral infection.
Binding on the releasing cell (autocrine) or neighboring cells (paracrine) triggers the production of antiviral proteins that interfere with virus replication.

Type II Interferon

Produced by immune cells only.
Similar function to type I interferon.
Also enhances macrophage ability and attracts neutrophils to the area.

Complement Cascade

Complement proteins are always present in the bloodstream.
Activated when they come in contact with a pathogen.
Often stimulated by antibodies from the Acquired immune system.
Stimulates a cascade of other complement proteins.
One cascade protein, the membrane attack complex (MAC), incorporates itself into the pathogen membrane, causing an inrush of fluids and disruption of cellular homeostasis.

Adaptive IS

Lymphocytes

Specialized Leukocytes (White Blood Cells).
Must be triggered by recognizing an antigen.
Each lymphocyte is specialized to recognize a single antigen (~100 million different antigens recognized per person).
Two main types: B cells & T cells (many subtypes): cytotoxic (killer) & helper.

Antigen

Can trigger an adaptive immune response against itself or a cell bearing it.
Usually proteins or large polysaccharides (sugars).
Often on the cell membrane of a pathogen.
Can also be unbound.

Generalized Adaptive Immune Response

Lymphocyte (B-cell or T-cell) encounters and binds to the antigen for which it is specialized.
Lymphocyte is activated: Clonal expansion of that lymphocyte (lots of cell division). All daughter cells also recognize the same antigen. Some daughter cells participate in the immune response. Others remain in the body and act as memory cells in case of further attack.
Lymphocytes and their secretions attack antigens: B cells differentiate into plasma cells and secrete antibodies which bind to the antigen, tagging it for attack by innate immune cells. Killer T cells directly attack cells bearing the antigen. After the antigen is eradicated, lymphocytes die so the immune system doesn’t become overly sensitive.

Primary Lymphoid Organs

The initial site of lymphocyte development.
Generally do not store naïve lymphocytes.

Secondary Lymphoid Organs

Naïve lymphocytes are stored and become activated once exposed to the appropriate antigen.

Lymphatic System

The lymphatic system accumulates cellular debris, including foreign antigens. The lymph nodes are specialized organs in which those antigens are recognized, and the cells of the immune system ramp up a response. Activated immune cells and antibodies flow out the efferent ducts of the lymph nodes and eventually back to the heart through the superior vena cava to be sent with the blood throughout the body in search of the “enemy.”

Lymphocyte Maturation

All lymphocytes are produced in bone marrow.
B cells mature in bone marrow.
T cells mature in the Thymus.
All mature lymphocytes are stored in secondary lymphoid organs.

Humoral-Mediated Immunity

B cells secrete antibodies which bind to the antigen and stimulate attack by phagocytes. Generally used for extracellular attack by bacteria, viruses, fungi, and toxins.

Cell-Mediated Immunity

T cells bind to the antigen directly and kill antigen-bearing cells with secreted chemicals. Generally used for intracellular attack by viruses or to destroy cancerous cells.

Helper T Cells

Activate both B cells and T cells through the release of cytokines.

NK Cells

A type of T-cell (Lymphocyte).
Target virus-infected cells and cancer cells.
Kill cells after binding directly to them.
Attack not mediated by antigens.
Often considered part of innate immunity.
Sometimes categorized as Adaptive Immunity.

Active Immunity

Recall that some B- and T-cells remain after an infection as memory cells. These memory cells allow for a rapid response to secondary exposure to an antigen. This is known as Active Immunity, the basis of all vaccines.

Passive Immunity

When antibodies from one individual are given to another individual. Occurs between mother and fetus in utero and mother and child through breast milk. Also used to treat some infections. Very short-lived protection (weeks or months).

Blood Typing

Red blood cells have carbohydrate chains on their cell surfaces that act as antigens.

Autoimmune Diseases

Mediated by autoantibodies and self-reactive T cells.

Practice Test

Not a kidney fx: constant comp. of urine at all times.
Basic renal process: Fluid moves by bulk flow from glomerular capillaries into Bowman’s space.
Filtered in Bowman’s capsule of a normal person: plasma protein.
Glomerular filtrate: similar to plasma, no pl. proteins though.
Correct about glom. fil. Hydrostatic pressure in BS opposes filtration.
Net glomerular filtration pressure: GFP = hydrostatic pressure in glomerular capillaries – hydrostatic pressure in Bowman’s capsule – osmotic force due to proteins in plasma.
Constriction of the afferent arterioles decreases hydrostatic pressure in glomerular capillaries.
TRUE regarding renal tubular reabsorption: reab. of glucose saturates at max trans. rate.
In what segment of the nephron is the greatest fraction of filtered water reabsorbed? Proximal tubule.
Which is NOT true about the countercurrent multiplier system of the kidney? The fraction of filtered NaCl reabsorbed from the ascending limb equals the fraction of filtered water reabsorbed from the descending limb.
In the condition diabetes mellitus, why does glucose appear in the urine? The filtered load of glucose becomes greater than the tubular maximum for its reabsorption.
Which is TRUE about the hormone vasopressin (also known as antidiuretic hormone, ADH)? It triggers the insertion of aquaporins into the apical membranes of collecting duct cells.
Salt in cereal: Urine osmolarity would decrease.
Stimulates vasopressin secretion: Increased plasma volume.
Sweat vs plasma donation: You will have a greater vasopressin secretion because sweat is hypo-osmotic to Plasma.
After prolonged exertion in a hot climate and heavy sweating, baroreceptors would decrease firing, leading to increased secretion of vasopressin and thus increased renal reabsorption of water.
TRUE regarding meiosis in a single germ cell: It results in 4 cells with 23 chromosomes each.
Spermatogenesis: results in four spermatozoa for every primary spermatocyte.
Testicular cancer of Sertoli cells: FSH secretion would be selectively inhibited, but LH secretion would be normal.
TRUE statement about events occurring in the menstrual cycle: Progesterone is low during the first half of the cycle and rises to a peak during the second half.
TRUE about the maturation of ovarian follicles: Growing follicles produce estrogen, which further stimulates follicle maturation.
A function of LH: stimulates androgen production by theca cells.
Estrogen in females is FALSE: In the presence of a high plasma concentration of progesterone, estrogen stimulates increased secretion of GnRH.
On day 14 of a typical 28-day ovarian and menstrual cycle, LH concentration in the blood will be at or near peak. The endometrium will be near the end of the prolif. phase. Estrogen concentration in the blood is relatively high.
During the early part of the ovarian cycle, FSH acts on granulosa cells, which convert androgens to estrogens. LH acts on theca cells, which synthesize androgens.
The corpus luteum persists in pregnancy because the implanting blastocyst secretes: human chorionic gonadotropin (hCG).
TRUE: Human chorionic gonadotropin maintains the corpus luteum.
Giving an agonist to the oxytocin receptor to a woman late in pregnancy: Onset of uterine contractions.
FALSE regarding oxytocin: It stimulates the synthesis of breast milk.
Hypothetical immunosuppressive drug: Vasodilation of local blood vessels.
Phagocytes and phagocytosis is TRUE: Contact of phagocytes with microbes stimulates the phagocytes to release chemicals that mediate the inflammatory response.
The bacteria Mycobacterium tuberculosis has the ability to prevent lysosomal fusion in macrophages. After phagocytosis, where would this microbe be found in the macrophage? Phagosomes.
Lupus: A drug that inhibits B cells.
Type O blood: Both anti-A and anti-B antibodies in the plasma blood-type.