Free MCAT study guide — Biological and Biochemical Foundations of Living Systems
The endocrine system is a critical MCAT topic that tests your understanding of hormonal signaling, feedback mechanisms, and the integration of physiology across organ systems. You need to know the major endocrine glands (hypothalamus, pituitary, thyroid, parathyroids, adrenal glands, pancreas, gonads, pineal gland), their hormones, target tissues, and physiological effects. The hypothalamic-pituitary axis is central: the hypothalamus releases releasing and inhibiting hormones that control the anterior pituitary, which in turn releases tropic hormones that stimulate peripheral glands. You must understand negative feedback loops (the primary regulatory mechanism) and rare positive feedback examples (oxytocin during labor, LH surge in ovulation). Hormone classification (peptide/protein, steroid, amino acid-derived) determines the signaling mechanism: water-soluble hormones bind surface receptors and use second messenger cascades, while lipid-soluble hormones (steroids, thyroid hormones) cross the membrane and act as transcription factors. The MCAT frequently presents clinical scenarios involving hormone excess or deficiency and asks you to predict physiological consequences.
The hypothalamus is the master regulator of the endocrine system, integrating neural and hormonal signals. It releases hormones into the hypophyseal portal system that reach the anterior pituitary. Key releasing hormones include GnRH (stimulates FSH and LH release), TRH (stimulates TSH release), CRH (stimulates ACTH release), and GHRH (stimulates growth hormone release). Inhibiting hormones include somatostatin (inhibits GH and TSH) and dopamine/PIH (inhibits prolactin). The anterior pituitary produces six hormones: FSH, LH, ACTH, TSH, GH, and prolactin. Remember with the mnemonic FLAT PIG (FSH, LH, ACTH, TSH, Prolactin, Ignore, GH). The posterior pituitary does not synthesize hormones -- it stores and releases oxytocin and ADH (vasopressin), which are synthesized in hypothalamic neurons and transported down their axons. Oxytocin stimulates uterine contractions during labor and milk letdown during breastfeeding. ADH increases water reabsorption in the collecting duct by inserting aquaporin-2 channels.
The thyroid gland produces T3 (triiodothyronine, the more active form) and T4 (thyroxine, the predominant circulating form that is converted to T3 peripherally). Synthesis requires iodine, which is actively transported into follicular cells by the sodium-iodide symporter. T3 and T4 are lipophilic (despite being amino acid-derived) and bind intracellular nuclear receptors to increase basal metabolic rate, oxygen consumption, heat production, and sympathetic nervous system sensitivity. Thyroid hormones are regulated by the HPT axis: TRH from the hypothalamus stimulates TSH from the anterior pituitary, which stimulates T3/T4 release. High T3/T4 inhibit TRH and TSH release (negative feedback). Hyperthyroidism (Graves disease, autoimmune stimulation of TSH receptor) causes weight loss, heat intolerance, tachycardia, and exophthalmos. Hypothyroidism (Hashimoto thyroiditis) causes weight gain, cold intolerance, fatigue, and myxedema. Calcitonin from thyroid parafollicular (C) cells lowers blood calcium by inhibiting osteoclasts (minor role in humans). Parathyroid hormone (PTH) from the parathyroid glands raises blood calcium by stimulating osteoclast activity, increasing renal calcium reabsorption, and promoting calcitriol (active vitamin D) production, which enhances intestinal calcium absorption.
The adrenal cortex has three zones producing three categories of steroid hormones (from cholesterol). The zona glomerulosa produces mineralocorticoids (primarily aldosterone), which increase sodium reabsorption and potassium secretion in the kidney, regulated by the RAAS system and serum potassium. The zona fasciculata produces glucocorticoids (primarily cortisol), which increase blood glucose through gluconeogenesis, suppress the immune system, and help the body respond to stress. Cortisol is regulated by the HPA axis (CRH -> ACTH -> cortisol). The zona reticularis produces adrenal androgens (DHEA). Remember the layers with GFR (glomerulosa, fasciculata, reticularis) and 'Salt, Sugar, Sex' for their products. The adrenal medulla is a modified sympathetic ganglion that releases catecholamines: epinephrine (80%) and norepinephrine (20%) in response to sympathetic stimulation. Epinephrine activates the fight-or-flight response: increases heart rate, blood pressure, bronchodilation, glycogenolysis, and lipolysis. Pheochromocytoma (adrenal medullary tumor) causes episodic hypertension, tachycardia, and sweating. Cushing syndrome results from chronic cortisol excess; Addison disease results from adrenal insufficiency.
The islets of Langerhans contain several cell types: beta cells produce insulin (the only hormone that lowers blood glucose), alpha cells produce glucagon (raises blood glucose), and delta cells produce somatostatin (inhibits both insulin and glucagon). Insulin is released in response to high blood glucose and promotes glucose uptake (via GLUT4 in muscle and adipose), glycogenesis, lipogenesis, protein synthesis, and cell growth. Insulin stimulates PFK-1 (glycolysis) and glycogen synthase, while inhibiting gluconeogenesis and glycogenolysis. Glucagon is released in response to low blood glucose and stimulates glycogenolysis, gluconeogenesis, and ketogenesis in the liver (glucagon receptors are primarily on hepatocytes). Type 1 diabetes is autoimmune destruction of beta cells (no insulin production), requiring exogenous insulin. Type 2 diabetes involves insulin resistance (cells respond poorly to insulin), often associated with obesity. Diabetic ketoacidosis (DKA) occurs in Type 1 when lack of insulin leads to uncontrolled lipolysis, excessive beta-oxidation, and ketone body accumulation.
The hypothalamic-pituitary-gonadal (HPG) axis regulates reproduction. GnRH from the hypothalamus stimulates FSH and LH release from the anterior pituitary. In males, FSH stimulates Sertoli cells (support spermatogenesis), and LH stimulates Leydig cells (produce testosterone). Testosterone promotes male secondary sexual characteristics, spermatogenesis, and muscle development, and inhibits GnRH/LH via negative feedback. Inhibin from Sertoli cells selectively inhibits FSH. In females, the menstrual cycle has three phases: follicular (days 1-14, FSH stimulates follicle development, rising estrogen), ovulation (day 14, LH surge triggered by positive feedback from high estrogen causes oocyte release), and luteal (days 14-28, the corpus luteum produces progesterone and estrogen to maintain the endometrium). If fertilization does not occur, the corpus luteum degenerates, progesterone drops, and menstruation begins. During pregnancy, hCG from the trophoblast maintains the corpus luteum until the placenta takes over progesterone production.
Hormones are classified by structure, which determines their signaling mechanism. Peptide/protein hormones (insulin, glucagon, GH, ADH, oxytocin, PTH) are water-soluble, travel freely in blood, bind cell surface receptors (GPCRs or RTKs), and use second messenger cascades for rapid effects (seconds to minutes). They are synthesized as preprohormones on the rough ER. Steroid hormones (cortisol, aldosterone, testosterone, estrogen, progesterone, vitamin D) are derived from cholesterol, are lipid-soluble, travel bound to carrier proteins (e.g., cortisol-binding globulin, sex hormone-binding globulin), cross the cell membrane, and bind intracellular/nuclear receptors that act as transcription factors for slower but longer-lasting effects (hours to days). Amino acid-derived hormones include catecholamines (epinephrine, norepinephrine -- water-soluble, act like peptide hormones) and thyroid hormones (T3, T4 -- lipophilic despite being amino acid-derived, act like steroid hormones with nuclear receptors). Only free (unbound) hormone is biologically active.
Anterior pituitary hormones: FSH, LH, ACTH, TSH, GH, Prolactin. Posterior pituitary: oxytocin, ADH.
The posterior pituitary stores and releases hormones synthesized in the hypothalamus.
Negative feedback: high peripheral hormone levels inhibit the hypothalamus and pituitary (e.g., cortisol inhibits CRH and ACTH).
Positive feedback examples: LH surge from high estrogen, oxytocin during labor.
T3 is more active than T4; T4 is converted to T3 in peripheral tissues.
PTH raises blood calcium; calcitonin lowers it. Remember: PTH = Parathyroid Hormone = Phosphate Trashing Hormone.
Adrenal cortex zones: Glomerulosa (aldosterone), Fasciculata (cortisol), Reticularis (androgens). 'Salt, Sugar, Sex.'
Insulin is the only hormone that lowers blood glucose; many hormones raise it (glucagon, cortisol, epinephrine, GH).
GLUT4 is insulin-dependent (muscle, adipose); GLUT2 is insulin-independent (liver, pancreatic beta cells).
LH surge causes ovulation; the corpus luteum produces progesterone to maintain the endometrium.
hCG maintains the corpus luteum in early pregnancy; it is the hormone detected by pregnancy tests.
Steroid hormones bind intracellular receptors; peptide hormones bind cell surface receptors.
Only free (unbound) hormone is active; binding proteins serve as a reservoir and extend half-life.
Confusing the anterior pituitary (synthesizes hormones) with the posterior pituitary (stores/releases hypothalamic hormones).
Forgetting that thyroid hormones are amino acid-derived but behave like steroid hormones (lipophilic, nuclear receptors).
Mixing up PTH (raises calcium) with calcitonin (lowers calcium) -- PTH is far more clinically significant.
Confusing primary endocrine disorders (gland dysfunction) with secondary (pituitary dysfunction) and tertiary (hypothalamic dysfunction) -- hormone levels will differ in each case.
Assuming insulin is released by alpha cells -- beta cells produce insulin, alpha cells produce glucagon.
Forgetting that the LH surge is caused by POSITIVE feedback from high estrogen, which is an exception to the usual negative feedback.
Confusing Cushing syndrome (cortisol excess: moon face, central obesity, hyperglycemia) with Addison disease (cortisol deficiency: hypotension, hyperpigmentation, hyponatremia).
Create a comprehensive hormone table with columns for gland, hormone, chemical class, target tissue, action, regulation (what stimulates/inhibits release), and associated diseases. This is the single most effective study tool for endocrine physiology. The MCAT often describes a clinical scenario (e.g., a patient with fatigue, weight gain, and elevated TSH) and asks you to identify the diagnosis and predict other lab values.
Practice feedback loop problems: given a primary gland disorder, predict the levels of hypothalamic releasing hormone, pituitary hormone, and peripheral hormone. For example, in primary hypothyroidism (thyroid gland failure): T3/T4 are low, so TSH is high (no negative feedback), and TRH is high. In secondary hypothyroidism (pituitary failure): TSH is low, T3/T4 are low, and TRH is high. Understanding these patterns is essential for MCAT passage-based questions involving endocrine pathology.
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