Pag. 1 a 10

SECTION 16 ENDOCRINOLOGY

HYPOTHALAMUS ORIGIN CONTROL TARGET

Supraoptic & Paraventricular Nuclei

Direct Innervation Posterior Pituitary

Arcuate nucleus (Median Eminence) Releasing Factors via Hypophysial Portal System

Anterior Pituitary

**Hypothalamus releases hormones ONLY to the Anterior Pituitary (Posterior Pituitary is controlled by nerves)

Hypothalamus Anterior Pituitary Hormones: o TRH (Thyrotropin Release Hormone) signals AP to release TSH o PRH (Prolactin Release Hormone) signals AP to release Prolactin o PIH (Prolactin Release Inhibiting Hormone) signals AP to stop Prolactin release o CRH (Corticotropin Releasing Hormone) signals AP to release ACTH to the Adrenal Gland o GnRH (Gonadotropin Releasing Hormone aka Luteinizing Hormone Release Hormone) signals AP to release FSH

and LH. o GHRH (Growth Hormone Releasing Hormone) and SS (Somatostatin); both affect AP Growth Hormone release,

with Somatostatin being negative feedback, inhibiting GH release.

Hypothalamus Posterior Pituitary Hormones: o Oxytocin: stimulates uterine contraction and induces labor. Improves uterine contractions, and controls post-

partum bleeding or hemorrhage. ADRs include water intoxication, NV, anaphylaxis, post-partum hemorrhage, uterine hypertonicity, fetal effects (e.g. bradycardia, neonatal jaundice, and premature ventricular contractions).

o Vasopressin (ADH): acts on distal renal tubular epithelium (promotes water reabsorption by increasing aquaporin channels at the CD membrane. Treats neurogenic diabetes insipidus, and post-op ab distention. ADRs include GI effects such as cramps, flatulence, NV, and CNS effects like tremor and sweating.

Pag. 2 a 10

ANTERIOR PITUITARY GLAND (aka Adenohypophysis)

HORMONE RELEASED TARGET TISSUE PHYSIOLOGICAL EFFECT(S)

TSH (Thyroid Stimulating Hormone)

Thyroid Adrenal Cortex

Production of Thyroid hormone

ACTH (Adrenocorticotropic Hormone)

Adrenal Cortex Production of adrenocorticoids e.g. Cortisol. Can be used for the diagnosis/differentiation of primary/secondary adrenal insufficiency.

(GH) Growth Hormone

Bones and Soft Tissue Growth of bones and soft tissue. Also stimulates protein, carb, and lipid metabolism to promote body growth.

(FSH) Follicle Stimulating Hormone

Female Ovaries Growth of Ovarian Follicle Estrogen Secretion

(LH) Luteinizing Hormone

Male Testes Female Ovaries

Sperm Production Ovary Ovulation & Estrogen and Progesterone secretion E.g. hMG (human menopausal gonadotropin), which have both FSH and LH activity.

Prolactin Male Testes Female Breasts

Testosterone Secretion Breast Development, milk secretion (galactorrhea) Made by lactotrope cells in AP, breast, and deciduas, causes lactation, sex gratification, immune tolerance of fetus in pregnancy, and stimulation of oligodendrocytes, which make myelin axon coatings.

POSTERIOR PITUIARY GLAND (aka Neurohypophysis)

HORMONE RELEASED TARGET TISSUE PHYSIOLOGICAL EFFECT(S)

Vasopression (ADH) Kidney Water retention, by increasing aquaporin channels at the collecting duct membrane

Oxytocin Uterus Breasts

Uterine contraction Milk Ejection

THYROID GLAND Makes T4, T3, and Calcitonin; signals metabolism for normal growth, tissue maintenance, and negative feedback of the Anterior Pituitary and Hypothalamus

o Thyroid Synthesis (4 stages)

Iodide concentrated at thyroid gland. Iodoperoxidase catalyzes iodination of tyrosine onto thyroglobulin, and couples iodinated tyrosine precursors. Proteolysis of thyroglobulin yields Thyroxine (T4) and Triiodothyronine (T3), in a 4:1 ratio (4x more weak T4 is made than strong T3).

T4 is converted to T3 at the liver and other organs. T3 enters target cells via membrane transport, binding to specific nuclear receptors for effect.

o T4 is weaker than T3, but has longer action duration 6-7 days instead of 1-2 days. Thyroid production is regulated by the Hypothalamic-Pituitary-Thyroid feedback loop. The synthesized T3 and T4 bind to sites in the AP, stopping the APs release of TSH, and thus stopping further Thyroxine production by the Thyroid. Examples of T3 and T4 sodium salts include Liotrix (Thyrolar), and Thyroid USP. Due to peripheral conversion, the blood levels convert to the 4:1 ratio.

Pag. 3 a 10

HYPERTHYROIDISM (aka Thyrotoxicosis) HYPOTHYROIDISM

Condition Graves Disease (diffuse toxic goiter) is the most common form, and autoimmune disorder, Abs bind and stimulate TSH receptors. Plummers Disease (toxic nodular goiter) causes excess thyroid production.

Hashimotos Thyroiditis a destructive autoimmune disease, common in elderly women. Excess thyroidectomy

Symptoms Tachycardia, goiter, nervous, irritability, profuse sweating, insomnia, weight loss

Cold, dry/flaky skin, coarse hair, slow speech, weight gain, low libido, constipation, HPT, bradycardia. Hypothyroid pregnant women may have suppressed ovulation causing infertility, thus requiring thyroxin (also needed for fetal brain development).

Treatment Control via anti-thyroid drugs, surgical thyroidectomy, or destroy tissue via radioactive isotopes. High concentration Iodide (Lugol solution) decreases iodide transport and thus synthesis of T3/T4. Lugol also shrinks the thyroid gland and firms it before surgery. Radioactive Iodine (131I), is trapped by the thyroid and incorporated into both tyrosine precursors and mature T3/T4. The beta particle decay causes localized thyroid destruction, dropping T3/T4 production. Thiourylenes inhibit iodoperoxidase, stopping the incorporation of iodine into tyrosine precursor molecules and preventing coupling of iodinated tyrosines to make T3 and T4. E.g. propylthiouracil, methimazole.

Thyroid upregulators mimic T3/T4 Give L-Thyroxin (T4).

Thyroid Function Tests:

1.) Serum Total Thyroxine (TT4) 2.) Serum Total Triiodothyronine (TT3) good early detection test 3.) Resin Triiodothyronine Uptake (RT3U) & Free Thyroxin Index (FTI)

FTI is an estimate of free T4 levels based on RT3U results. 4.) Serum TSH Assay

o Calcitonin is a peptide hormone made by Parafollicular Cells (C-Cells) of the Thyroid.

Functions to LOWER blood [Ca], by inhibiting gut Ca absorption, inhibiting osteoclast activity, and inhibiting renal tubular reabsorption of Ca.

Secretion triggered by high serum [Ca] and Gastrin. Thus opposes the action of PTH, which RAISES blood [Ca]. Calcitonin not very significant in human Ca

regulation.

PARATHYROID GLANDS o 4 tiny glands on thyroid surface. Has Chief Cells, which make PTH, role to increase blood [Ca]. o PTH binds to PTH1 receptor at bones, inhibiting osteoblast activity but leaving osteoclasts to continue (dont

have PTH1 receptor). Osteoblast RANKL expression increases, with OPG expression decreasing (OPG normally binds/neutralizes RANKL). Without OPG, RANKL binds RANK, allowing increased osteoclast formation and bone resorption.

o PTH also binds at the kidney, enhancing Ca and Mg reabsorption at the DCT. o PTH also increases kidney production of activated Vit D, which in turn signals Calbindin to increase Ca

absorption at the intestines. (Bone is Hydroxyapetite, CaPO4) o HyperPTH = excess blood [Ca], low blood [PO4], muscle atrophy/fatigue. o HypoPTH = low blood [Ca], high blood [PO4], convulsions, hypokalemia, neuromuscular irritability.

Pag. 4 a 10

ADRENAL GLANDS (on top of kidneys) release hormones in response to stress

HORMONE PRODUCED

TARGET ORGAN

PHYSIOLOGICAL ACTION

ADRENAL CORTEX (outside)

Corticosteroids, Androgens,

Mineralocorticoids

Adrenal Gland

ACTH regulates Adrenal secretion of Adrenocorticoids (Mineralocorticoids + Glucocorticoids) Mineralocorticoids (Aldosterone) retains Na/water, excrete K. Glucocorticoids (Cortisol and Cortisone) controls glucose metabolism and protein synthesis, also have anti-inflammatory action. Androgens male sex hormone precursors DHEA, DHEA-S, and Androstenedione (testosterone precursor)

ADRENAL MEDULLA

(inside)

Adrenaline (Epi) Norepinephrine

Vasculature, Organs

Epinephrine increases BP, HR, vasoconstriction, and skeletal muscle blood supply. Norepinephrine increases effects of epinephrine

o Addisons Disease: Chronic adrenal insufficiency (hypocortisolism)

Low adrenal glucocorticoids and mineralocorticoids. Caused by HIV, TB, auto-immunity. Symptoms include weakness, fatigue, weight loss, NV. Treat with replacement cortisol (e.g. Fludrocortisone).

o Cushing Syndrome: Chronic adrenal excess hypercortisolism / hyperadrenocorticism High levels of blood cortisol, causing rapid weight gain, Moon Face, Buffalo Hump (central obesity), low libido,

easy bruising. Treat by removing adrenals and post-op replacement steroids (HC or Prednisolone). Can also lead to insulin resistance (Type 2 diabetes), HPT, and excessive bone resorption (osteoporosis).

Exogenous (Iatrogenic) Cushing Syndrome when glucocorticoids are prescribed for asthma, RA, transplant. Endogenous Cushing Syndrome due to bodily change:

Pituitary Cushings: Pituitary adenoma secretes ACTH

Adrenal Cushings: Excess cortisol made by adrenal gland tumors

Desirable adrenocorticoids mimic natural glucocorticoid activity (metabolic, anti-inflammatory, immunosuppressive), and provide feedback regulation of pituitary corticotrophin. Indications for replacement therapy include acute/chronic adrenal insufficiency for Addison or Cushing syndrome. Last line for severe arthritis. Also used for inflammatory ocular disorders, chronic ulcerative colitis, cerebral edema, skin disorders, etc. ADRs include suppression of the HPA axis. CNS effects include headache, vertigo, increased IOP, muscle fatigue, etc.

Pag. 5 a 10

PANCREAS o Acini Cells: produce digestive enzymes o Islet of Langerhans Cells: alpha/beta/delta cells

ALPHA cells = make Glucagon for signaling Glycogenolysis @ Liver to free blood glucose. BETA cells = make peptide Insulin, which is stored in vesicles with Zinc.

INSULIN ROLES

INCREASED: DECREASED:

-Increased Glycogen (storage) synthesis at liver and muscles -Increased Lipid synthesis (fat cells take in blood lipids) -Increased Esterification of fatty acids to make fats -Increased Amino acid uptake -Increased Potassium uptake -Increased arterial wall relaxation for increased bloodflow. -Increased HCl secretion by Parietal Cells

-Decreased Proteolysis -Decreased Lipolysis (Ketogenesis) -Decreased Gluconeogenesis -Decreased Autophagy (degradation of damaged organelles) -Decreased Na renal excretion Ketogenesis: **When blood glucose low, fatty acids are broken yielding Acetone and Acetyl CoA (for Krebs Cycle) (Acetone smells sweet)

DELTA cells = make Somatostatin.

o Diabetes Insipidus CNS problem (Vasopressin/ADH insufficiency), causes huge dilute urine loss. Treat with ADH.

Central D.I = caused by Hypothalamus dysfunction (tumor, trauma, etc). Neprhogenic D.I = kidneys are unresponsive to ADH.

o Diabetis Mellitus insulin deficiency or resistance. Cells are starved of glucose, with hyperglycemic blood. Causes

hunger, polyuria causing polydipsia (thirst). Prevent via routine screening. Risk factors include weight, HPN, cholesterol, and smoking. Insulin deficiency causes hyperglycemia, causing cataracts, retinopathy, nephropathy, neuropathy, atheroma, numbness, proteinuria, CRF (Chronic Renal Failure), gangrene of extremities, etc. Insulin Dependent DM (Type 1) auto-immune attack on Islet cells, no insulin at all. Non-Insulin Dependent DM (Type 2) arises from insulin resistance, where the fat, muscle, and liver cells

dont respond strongly to insulin and cant uptake glucose. Develops slowly over time, starting from adolescence. Risk factors are FH, ages over 45, sedentary lifestyle, poor diet, obesity, diabetes during previous pregnancies, HDL under 35 mg/dL, high levels of triglycerides, metabolic syndrome, and polycystic ovarian syndrome. As well, ethnic groups of African Americans, Hispanic Americans, Asian and Native Americans have higher risk.

Secondary Diabetes (e.g. Pancreatic Disease) Impaired Glucose Tolerance Gestational Diabetes occurs during 3rd trimester; insulin receptors dont function properly due to presence of

placental lactagen interfering with insulin receptors.

Pag. 6 a 10

o Anti-Diabetic Agents:

Insulin: peptide made of 2 polypeptides, A-Chain (21AA) and B-Chain (30AA), connected by disulfide bonds,

with a 3rd disulfide double bond within A. Recombinant insulin (Humulin) and porcine converted (Novolin). Five synthetics exist, in 3 categories based on onset/duration/intensity after SUBCUTANEOUS administration. Solubility at injection site depends on physical state, zinc content, buffer, and protein content:

SHORT ACTING INSULINS: (all mods to start/end of B-Chain); compared to regular insulin, SA insulins are less likely to cause hypoglycemia, and thus dont need snacks between meals) o Lispro LYS29 and PRO28 of B-chain are reversed; onset 15-30 minutes/3-4 hour duration o Aspart PRO28 of B-chain replaced with ASP; hinders hexamer formation = faster onset, shorter

duration. o Glu-Lisine also 2 AA replacements, rapid onset and short duration. ASP on B-3 replaced with LYS, and

LYS on B29 replaced with GLU.

INTERMEDIATE ACTING INSULINS: o Isophane (NPH): complex complexed with protamine (fish protein) in phosphate buffer. Protamine

enhances aggregation of insulin into dimmers and hexamers after S/C injection, thus increasing duration.

o Lispro / Aspart: also available as combination products with protamine complexes.

LONG ACTING INSULINS: o Insulin Glargine (Lantus) is long acting. ASN21 on A-chain is replaced by a GLY, with a dipeptide ARG-

ARG replacing THR30 on the B-Chain. Both decrease solubility at the physiological pH, causing precipitation and delayed absorption after S/C injection. A once/daily injection yields a constant concentration/time profile that closely mimics endogenous basal rate insulin secretion.

o Insulin Detemir (Levemir) is long acting. 14C fatty acid chain is covalently bonded to LYS29 of the B-Chain, with THR30 of the B-Chain removed. Via this fatty acid chain, it binds to albumin in blood, slowly dissociating from this complex.

Sulfonylureas: work by blocking ATP-sensitive K-channels, which stimulate insulin release from Beta Cells. Also

enhance insulin response by increasing affinity of cell surface insulin receptors.

1st Generation Sulfonylureas: Tolbutamide, Chlorpropamide, Tolazamide, Acetohexamide

2nd Generation Sulfonylureas: Glyburide, Glipizide, Glimepiride *All have larger groups attached to their aromatic rings = better lipid solubility and potency

ADRs: GI effects (NV, diarrhea, constipation), hypersensitivity (skin, photo), blood dyscrasias (leucopenia, thrombocytopenia, etc), cholestatic jaundice, and hyponatremia (due to ADH). **Sulfonylureas are highly plasma protein bound, metabolized by CYP P450. Interactions occur with other K-channel openers (Minoxidil, Diazoxide), drugs causing plasma protein displacement (fibrates, sulfonamides, phenylbutazone), and CYP P450 interacting drugs.

Pag. 7 a 10

Metformin (biguanide): increases insulin action in peripheral tissues and inhibits hepatic gluconeogenesis. Work by increasing glucose transport across skeletal muscle cell membranes. ADRs may cause lactic acidosis, metallic taste, GI effects (NV, diarrhea, anorexia). **Higher risk of lactic acidosis and acute renal failure can occur if Metformin is given with corticosteroids, iodinated materials, or other cationic drugs renally secreted, as they may interfere with Metformins renal tubular secretion

Meglitinides: stimulate more insulin release, faster onset and shorter duration than Sulfonylureas. Includes Repaglinide and Nateglinide. ADRs: hypoglycemia, URTI, rhinitis, bronchitis, headaches, back pain. **Possible interactions with other CYP drugs.

Rosiglitazone/Pioglitazone (Thiazolidinediones): Bind to PPARs (Nuclear Peroxisome Proliferator Activated Receptors), which controls the transcription of insulin responsive genes, adipocyte differentiation, and lipid metabolism. They work to enhance the synthesis/translocation of glucose transporter proteins, enhance insulin sensitivity, and better fat redistribution, thus decreasing insulin resistance and improving target cell response to insulin. These ONLY WORK IF insulin is ALREADY PRESENT, as they only increase insulin sensitivity and are not related to actual insulin production. ADRs: hepatotoxicity, GI effects, weight gain/edema, headache. **Possible interactions with other CYP drugs.

Alpha-Glucosidase Inhibitor: inhibit carbohydrate digestion in the small intestine, thus limiting post prandial blood glucose increases. Structural analogs of mono/polysaccharides. Miglitol has better oral absorption than Acarbose. ADR: GI distress due to undigested carbohydrates. **May impair oral digoxin absorption.

Peptide Mimetics: works WITH insulin or anti-diabetic agents Exenatide: mimics Incretin, which are endogenous compounds that improve glycemic control (e.g.

Glucagon-Like Peptide, GLP-1). Enhances beta cell insulin secretion, suppressing glucagon secretion, and slowing gastric emptying. Helps improve glycemic control. ADRs: CNS effects and GI effects.

Pramlintide: analog of human Amylin, made by beta cells in response to food. Amylin slows gastric emptying, thus allowing slower more constant glucose absorption from the small intestine. It also suppresses glucagon secretion and modulates appetite and caloric intake. Used in both Type 1 & 2 diabetes. ADRs: allergic reaction, CNS and respiratory effects. **May decrease rate/extent of oral absorption of other drugs due to slowed gastric emptying, thus avoid other gastric motility modifying drugs (anti-muscarinics).

o Glucose Drug Interactions:

DRUG: ACTION:

Thiazides Increase blood glucose

Beta Blockers Inhibit glycogenolysis and glucagon release, thus hypoglycemic. It can also promote hyperglycemia by inhibiting insulin secretion and decreasing insulin tissue sensitivity.

Oral Contraceptives & Glucocorticoids

Decreases anti-diabetic agent efficacy by increasing insulin resistance. Glucocorticoids also have metabolic effects that oppose insulin.

Androgens & Anabolic Steroids

Can cause hypoglycemia in diabetics.

Monoamine Oxidase Inhibitors

Stimulate insulin secretion, possibly causing hypoglycemia.

Pag. 8 a 10

OTHER ENDOCRINE GLANDS

GLAND HORMONE RELEASED TARGET TISSUE PHYSIOLOGICAL EFFECT(S)

PINEAL GLAND Melatonin Dimethyl tryptamine

AP, reproductive organs, etc.

Circadian sleep cycle in response to darkness. P

THYMUS Thymosin T-cells Enhances T-cell production

GONADS

TESTES: Testosterone

Male Sex Organs and body

Spermatogenesis, sex characteristics development, sex drive

OVARIES: Estrogen Progesterone

Female sex Organs and body Uterus

Stimulates uterine and breast growth, sex characteristics Pregnancy preparation; prepares uterus lining for fertilized egg implantation, readies mammary glands for milk production.

OVULATION CYCLE &MENSTRUATION o During Menstrual cycle, estrogen is produced by ovarian follicles. o After ovulation, estrogen made by Corpus Luteum , a temporary structure that makes estrogen and progesterone. o During pregnancy, ovulation doesnt occur suppressed by high levels of estrogen and progesterone (MOA of

oral contraceptives). o HCG (Human Chorionic Gonadotropin) levels are higher in first 3 months of pregnancy. o Progestins during pregnancy made by ovaries, corpus luteum, and placenta.

o Body temperature is higher during LUTEAL PHASE. o Ovary at beginning of LUTEAL PHASE is the Corpus Luteum.

Pag. 9 a 10

o Menopause starts when ovaries stop making estrogen, around 51 years of age. Common causes include hot flushes, night sweat, mood swings, sleeplessness, and lethargy. Depression, urogenital atropy may also occur.

o Releases Thymosin, which signals T-cells to produce more T-cells. o Dysmenorrhea: menstrual pains, occur 20-25 years. Primary if no underlying cause, Secondary if the cause is a

gynecological disorder. o Endometriosis: a common cause of Secondary Dysmenorrhea, causes pelvic pain, spotting before normal Period,

and may cause infertility.

GONADAL HORMONES

17-Beta-Estradiol

o ESTROGEN: Unlike other steroids, estrogens have an aromatic A-ring. Estradiol is the principle estrogenic hormone, existing in equilibrium with estrone, which is converted to estriol before excretion. Routes include Oral/Vaginal/Patches/Topical/Injections. Estradiol Esters for IM oily injections are slowly hydrolyzed in muscle to estradiol before systemic absorption. Some 17-alpha-ethinyl estradiols increase 1st Pass metabolism, increasing oral efficacy, including ethinyl estradiol and mestranol. Conjugated estrogens are oral mixtures of estrogen metabolites Premarin, Cenestin, Menest, Enjuvia, and Estropipate. Estrogen is very specific to estrogen receptors (intracellular, affecting gene transcription). Estrogen can be used for oral contraception, treatment of menopausal symptoms, acne, osteoporosis, or prostate cancer. ADRs include GI, CV, fluid/electrolyte disturbances, and greater risks of endometrial cancer.

o ANTI-ESTROGENS: Non-steroidal estrogen antagonists. Include Clomiphene, Tamoxifen citrate, and Toremifene citrate. Inhibit estrogen activity by competitively binding to estrogen receptors ONLY in breast tissue, thus treating estrogen-dependent breast cancer. Clomiphene can induce ovulation in those with ovulation failure.

o AROMATASE INHIBITORS: Anastrozole (Arimidex) and Letrozole (Femara) are non-steroidal inhibitors of Aromatase. Exemestane (Aromasin) is a steroidal inhibitor of aromatase. Aromatase is an enzyme that converts Androgens (Androstenedione & Testosterone) to estrogens (estrone and estradiol). Aromatase Inhibitors thus used to treat advanced breast cancer.

o SELECTIVE ESTROGEN RECEPTOR MODULATORS: Raloxifene (Evista) is a SERM. It has agonist effects on estrogen

receptors at bone/lipids, but antagonist effects at uterine/breast tissues. Thus, it can prevent osteoporosis while also having no effect on breast cancers. **Estrogen binding at bone inhibits osteoclast activity**

Pag. 10 a 10

o PROGESTINS: (FORMS OF PROGESTERONE)

Progestins work similarly to estrogen, binding progesterone receptors to change mRNA synthesis. Mainly used as oral contraceptives, and given alone or with estrogens as mono/bi/triphasic combinations (E.g. Plan B, Levo-Norgestrel). They can also decrease excessive menstrual bleeding or endometriosis. ADRs weight gain, edema, breast CA exacerbation, irregular menses, etc. 17-Alpha-OH-Progesterone: C6 methyl and C17 acetoxyl increase lipid solubility and decrease 1st Pass

Metabolism, enhancing oral activity and progestin effects. 19-Nortestosterone: classed as an androgen, lacks a 19-methyl group, thus increasing progestational activity

(e.g. Norethynodrel, Norgestimate, Etonogestrel (NuvaRing)). Drospirenone (Yasmin): oral contraceptive combined with ethinyl estradiol, structurall different than other

progestins.

o ANTI-PROGESTINS: Mifepristone (Mifeprex) is a steroidal progestin receptor blocker, used to terminate pregnancy during first 49 days. After 2 days, Misprostol then given which induces uterine contractions. Used to terminate intrauterine pregnancies.

o ANDROGENS & ANABOLIC STEROIDS: testosterone is the primary androgen, with two effects: Androgenic Effects: prodrugs Delatestryl and Depo-Testosterone, both IM, long action due to slow ester

hydrolysis. 17-alpha-methyl = potent, orally active forms like Methyltestosterone and Fluoxymesterone. 17-alpha group decreases 1st pass metabolism.

Anabolic Effects: utilize a 17-alpha modification, including oxymetholone, nandrolone, and oxandrolone. Testosterone is converted to DHT in the cytoplasm by 5-alpha-reductase, which then binds nucleus androgen receptors, effecting genetic change.

Testosterone

Testosterone is used for androgen replacement therapy, treating breast CA and endometriosis, female hypopituitarism, anabolic therapy, and anemia.

o ANTI-ANDROGENS: competitively bind androgen receptors, help treat prostate cancer. Non-steroidal, include Flutamide, Bicalutamide, and Nilutamide.

o 5-ALPHA-REDUCTASE INHIBITORS: competitively inhibit 5-alpha-reductase, which converts testosterone to potent DHT, which causes Benign Prostatic Hyperplasia.