10.1 The male axis #
10.1.1 GnRH, the gonadotrophins, and the testis #
GnRH is released in pulses, about once an hour in an adult man. Continuous exposure desensitises the gonadotroph, and LH and FSH fall. LH follows the pulses and acts on Leydig cells, which make testosterone. FSH acts on Sertoli cells, which support germ cells, secrete androgen-binding protein so local testosterone stays high, and secrete inhibin B, the selective feedback on FSH. Testosterone feeds back on LH and GnRH. Spermatogenesis needs both the FSH-supported Sertoli cell and a high local testosterone.
Spermatogonia divide outside the blood–testis barrier of Sertoli tight junctions. Meiosis, which Cell Biology and Developmental Biology describe, produces spermatids, and spermiogenesis builds the acrosome, flagellum, and condensed nucleus. The line takes about 70 days. Sperm mature and are stored in the epididymis. The ejaculate volume is mostly seminal vesicle and prostate; sperm are a small fraction. Capacitation occurs in the female tract. Fertilisation belongs to Developmental Biology.
Spermatogenesis runs about 2–3°C below core temperature. The pampiniform plexus is a countercurrent heat exchanger: venous blood cools the incoming artery, the same geometry as the vasa recta, used here for heat. Failure of descent leaves the testis at core temperature and impairs sperm production. In some targets, 5α-reductase converts testosterone to dihydrotestosterone. Aromatase makes a fraction into oestradiol, which contributes to male bone maturation as well.
Erection is parasympathetic: nitric oxide raises cGMP, helicine arteries dilate, and the filling sinusoids compress venous outflow. Emission is sympathetic. Ejaculation is somatic, through the pudendal nerves. One organ uses all three outflows.
10.2 The menstrual cycle #
10.2.1 The follicular phase and the two-cell model #
A textbook cycle is about 28 days, ovulation near the middle, and the luteal phase the steadier half, about 14 days. Real cycles vary. Most mammals do not menstruate; they reabsorb the endometrium in an oestrous cycle. Menstruation is mainly a primate pattern. The skeleton — follicle, ovulation, corpus luteum — is the general mammalian one.
FSH recruits a cohort of antral follicles. In the two-cell arrangement, theca cells under LH make androgens, and granulosa cells under FSH aromatise them to oestradiol. Rising oestradiol and inhibin lower FSH. The dominant follicle survives the fall because it has more FSH receptors; the rest of the cohort regresses. Oestradiol proliferates the endometrium and makes cervical mucus penetrable by sperm.
10.2.2 The LH surge #
For most of the cycle, oestradiol inhibits LH. When oestradiol has been high for about two days and progesterone is still low, the sign reverses at hypothalamus and pituitary. Sensitivity to GnRH rises, and the LH surge follows. A progesterone-dominated background, as in the luteal phase, prevents the switch. Ovulation follows about a day and a half later. The oocyte completes the first meiotic division. Proteases and prostaglandins weaken the follicle wall; it is not simply burst by pressure. The surge also luteinises the granulosa, which turns toward progesterone. Positive feedback stops because ovulation removes the oestradiol signal that caused it, and rising progesterone restores negative feedback.
10.2.3 The luteal phase and menstruation #
The corpus luteum makes progesterone and oestradiol under LH. Progesterone converts the endometrium to a secretory form, raises basal temperature by a few tenths of a degree, thickens cervical mucus, and holds FSH and LH down so that another ovulation does not occur. Unless pregnancy rescues it, the corpus luteum lasts about 14 days. In sheep and many other mammals the uterus signals luteolysis with prostaglandin F2α, delivered locally by a vein-to-artery countercurrent. In women the lifespan is largely intrinsic; removing the uterus does not save the corpus luteum in that way. When progesterone and oestradiol fall, spiral arteries constrict, the functional endometrium is shed, and FSH begins to rise for the next cohort. The positive-feedback window cannot reopen until a new follicle has held oestradiol high, which luteal progesterone had made impossible.
10.3 Pregnancy, birth, and milk #
10.3.1 hCG and the placenta #
The corpus luteum is due to regress at about 14 days, which would shed the endometrium. The syncytiotrophoblast secretes hCG, which binds the LH receptor, lasts longer in blood than LH, and maintains the corpus luteum. hCG is present from around implantation and peaks in the first trimester. By about 8–10 weeks the placenta makes enough progesterone that the corpus luteum can regress. That luteal–placental shift is why the ovary is essential early and not later for progesterone.
The placenta makes progesterone from maternal cholesterol. It cannot complete oestrogen synthesis alone. The fetal adrenal supplies androgen precursor, and placental aromatase makes the oestrogens, especially oestriol. Production therefore reports on fetus and placenta together, the fetoplacental unit. Human placental lactogen rises through pregnancy, reduces maternal insulin sensitivity, and promotes maternal use of fat, leaving a larger share of glucose for the fetus.
Maternal blood volume and cardiac output rise by roughly a third to a half. Progesterone drives ventilation, arterial PCO2 falls to about 30 mmHg, and the kidney lowers bicarbonate so pH stays near normal: a compensated respiratory alkalosis. Fetal gas exchange is placental. The ductus venosus, foramen ovale, and ductus arteriosus bypass the unventilated lungs. At birth, lung inflation and rising PO2 lower pulmonary resistance, the foramen ovale is pressed shut, and the ductus arteriosus closes as oxygen rises and the prostaglandins that held it open fall. How the shunts form is Developmental Biology. The pressure and oxygen logic is physiology.
10.3.2 Parturition as positive feedback #
Species differ in the trigger. In sheep, fetal cortisol shifts placental steroid metabolism so maternal progesterone falls and oestrogen rises, and labour follows. Human maternal progesterone stays high into labour. What changes is myometrial sensitivity: oxytocin receptors and gap junctions increase, so the uterus can contract as a single-unit smooth muscle, local progesterone action is functionally withdrawn, and prostaglandins from the membranes soften the cervix and promote contraction. Fetal cortisol in the human matters for surfactant. It is not the single ovine switch.
Once contractions are established, the Ferguson reflex is the positive feedback. Cervical stretch releases oxytocin, contraction increases, and stretch increases again. Delivery removes the stretch, and expulsion of the placenta removes the local prostaglandin source. The loop is safe because it ends. These notes stop at that control.
10.3.3 Prolactin and oxytocin #
Oestrogen and progesterone prepare the breast and, while high, restrain full secretion. After delivery they fall, and prolactin acts. Prolactin is under tonic dopamine inhibition. Suckling removes that inhibition and causes a prolactin pulse, which maintains synthesis. Oxytocin does not make the milk. It contracts myoepithelial cells and ejects it. Suckling releases oxytocin, and so can the conditioned sight or sound of the infant, a learned feed-forward limb. Synthesis and ejection can fail separately because the controls are separate. The ejection reflex stops when suckling stops. While prolactin is high and suckling frequent, GnRH pulses are suppressed and ovulation is often suspended. That is a consequence of the axis, not an instruction.
10.4 Exercise as one integrative example #
10.4.1 Circulation and breathing #
The numbers are a representative healthy adult, rounded so the arithmetic is visible, not a training target. At rest: heart rate about 70, stroke volume about 70 mL, output about 5 L/min, oxygen uptake about 250 mL/min from an arteriovenous difference of about 50 mL/L, minute ventilation about 7.5 L/min, alveolar ventilation about 5 L/min, arterial PCO2 about 40 mmHg and PO2 about 95.
At the onset, before metabolites circulate, central command raises heart rate and ventilation. This is feed-forward. Vagal withdrawal acts within a beat; sympathetic drive then adds rate and contractility. The baroreceptor operating point is reset upward, so the rise in pressure does not reflexly slow the heart. The muscle pump, the respiratory pump, and venoconstriction raise venous return. Starling’s law and a rise in contractility both increase stroke volume. Output can reach about 20 L/min, and more in a trained person. Stroke volume plateaus; further gains are mostly rate.
Total peripheral resistance falls. Metabolites in working muscle — adenosine, potassium, H+, CO2, nitric oxide — override sympathetic vasoconstriction, a functional sympatholysis. Kidney, gut, and inactive muscle do constrict, so a larger share of a larger output reaches active muscle. Mean pressure rises only modestly, because output and the fall in resistance nearly match. Pulse pressure widens. Coronary flow rises with cardiac work and is still mostly diastolic, now in a shorter diastole. Cerebral flow stays near 750 mL/min. Skin flow waits on the heat load.
| Variable | In moderate dynamic exercise | Why |
|---|---|---|
| Heart rate | Up | Vagal withdrawal, then sympathetic drive; baroreflex reset |
| Stroke volume | Up, then a plateau | Muscle pump, Starling, contractility |
| Cardiac output | Up several-fold | The product |
| Total peripheral resistance | Down | Local vasodilatation in active muscle |
| Mean arterial pressure | Up modestly | Output rises at least as much as resistance falls |
| Arterial PCO2 and PO2 | Nearly unchanged | Ventilation matched to CO2 output |
| Mixed venous PO2 | Down | Wider extraction |
| Renal and splanchnic flow | Down | Sympathetic vasoconstriction |
Ventilation rises in proportion to CO2 production, so in moderate work arterial PCO2 stays near 40 mmHg and arterial PO2 near its resting value. The drive is not a prior rise in arterial PCO2. Central command, muscle afferents, a rise in potassium and temperature, and the chemoreceptors set a ventilation that matches CO2 output, which is feed-forward with a chemical trim. If PCO2 were the only stimulus, it would have to rise before ventilation did.
A representative heavy uptake of about 3 L/min at an output of 20 L/min requires an arteriovenous oxygen difference of about 150 mL/L: arterial content still about 200 mL/L, mixed venous content down near 50. The Bohr effect in hot, acid, hypercapnic muscle helps that unloading. At sea level in health, arterial haemoglobin stays nearly saturated. The ceiling is output and extraction, not ventilation. In exhausting work, lactate and H+ rise, ventilation increases further, arterial PCO2 can fall a little, and pH can fall below 7.2. The carotid bodies now have an acid stimulus they did not have in moderate work.
10.4.2 Fuel, heat, and fluid #
The first seconds use phosphocreatine. Early work uses muscle glycogen. As work continues, blood glucose and fatty acids take over. Sympathetic activity lowers insulin despite a normal glucose, so the liver can produce glucose under glucagon and adrenaline. Muscle still takes glucose up, because contraction moves GLUT4 by an insulin-independent path. That split holds plasma glucose steady in ordinary work. In very prolonged work, liver glycogen can fail and glucose falls. Growth hormone and cortisol add lipolysis if the work lasts into their slower time course.
Most of the energy becomes heat. Core temperature rises. The set point does not: this is not fever. Sweating and cutaneous vasodilatation answer an error. Skin flow can reach several litres a minute and then competes with muscle. In hot heavy work, venous return is also threatened by blood pooled in skin veins. Sweat is hypotonic, so prolonged sweating lowers volume and raises osmolarity. ADH and thirst rise, and aldosterone, with heat acclimatisation of the sweat gland, lowers later sweat sodium. Earlier sweating, more dilute sweat, a larger plasma volume, and a lower heart rate at the same load, over days of heat exposure, are acclimatisation. Nothing heritable has changed.
When work stops, heart rate falls promptly as the vagus returns, then more slowly as metabolites, heat, and catecholamines settle. Oxygen consumption stays above rest while phosphocreatine and oxygen stores are restored. A fall in blood volume, as distinct from exercise, would use the same parts differently and is not a second worked example: baroreceptor unloading would raise rate and resistance, a lower capillary pressure would draw interstitial fluid into plasma while the Starling balance allowed it, and ADH with the renin–angiotensin–aldosterone system would conserve water and sodium. Exercise is the example that also forces breathing and metabolism to declare themselves.
10.5 Key terms, summary, and self-check #
Key terms. GnRH pulse; Leydig cell; Sertoli cell; two-cell model; LH surge; corpus luteum; hCG; fetoplacental unit; Ferguson reflex; prolactin; oxytocin; central command; functional sympatholysis; Fick principle.
Summary. Pulsatile GnRH sets LH, which drives Leydig-cell testosterone, and FSH, which supports Sertoli cells and spermatogenesis. Follicular oestradiol, made by theca and granulosa together, flips from negative to positive feedback and triggers the LH surge; luteal progesterone then holds the endometrium until the corpus luteum regresses or hCG rescues it. The placenta takes over the steroids. Parturition is an oxytocin positive-feedback loop that delivery ends. Prolactin makes milk and oxytocin ejects it. Moderate exercise raises output by rate, Starling, and contractility, lowers resistance in the muscle that is working, and raises ventilation in proportion to CO2 so that arterial gases barely change. A reset baroreflex permits the higher pressure, and a low-insulin, high-glucagon pattern supplies fuel while heat is lost without a change in temperature set point.
Self-check.
1. What does LH do in the testis, what does FSH do, and why must GnRH be pulsatile?
2. Why is the LH surge positive feedback, and what ends it?
3. What does hCG do in the first weeks, and what takes over that job?
4. How do prolactin and oxytocin divide lactation?
5. In moderate exercise, output and ventilation both rise several-fold. Why does arterial PCO2 stay near 40 mmHg?
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# Closing: how the chapters fit together
Chapter 1 is the grammar: a sensor, a comparison, an effector, a sign, and a way to stop. Chapters 2 and 3 are the effectors that grammar uses — the three kinds of muscle, the two autonomic outflows, and the hypothalamic–pituitary map. Insulin is a deliberate exception to that map, and ADH and oxytocin are neural releases rather than portal-controlled products. Chapters 4 and 5 move what cells need, convection first and diffusion at the capillary and the alveolus. The fish gill and the bird lung are there so that a tidal alveolar pool is seen as one solution, not as the definition of gas exchange. Chapter 6 is the fluid being moved, and the self-limited cascade that stops the circuit emptying. Chapter 7 is intake, arranged so the liver sees sugars and amino acids first and most fat does not. Chapter 8 is the long-term defence of volume, osmolarity, and pH, and therefore the long-term setter of the pressure that Chapter 4 only buffers. Chapter 9 puts chemical signals on fuel, growth, calcium, and the permission to respond to catecholamines. Chapter 10 uses the set twice: once to time reproduction, where positive feedback is supposed to run to completion, and once in exercise, where negative feedback, feed-forward, and a reset reference operate together.
Countercurrent exchange is how a gill holds an oxygen gradient, how the vasa recta avoid destroying a salt gradient, and how the pampiniform plexus cools arterial blood. A portal circulation is how the hypothalamus talks to the anterior pituitary and how the intestine talks to the liver. A positive-feedback loop is safe in an action potential, a clot, an LH surge, and a birth only because each contains its own ending.
Revision checklist #
1. Draw the glucose, temperature, and blood-pressure loops, and mark which limb of pressure control is slow.
2. State the size principle, where cardiac muscle sits on the length–tension curve, and the calcium switch in smooth versus skeletal muscle.
3. Name the transmitter at a ganglion, at a parasympathetic organ, and at a typical sympathetic organ, and list the six anterior pituitary hormones with their hypothalamic controls.
4. Walk the left ventricle through one cycle with the valve states, and write cardiac output both as rate times stroke volume and as the Fick relation.
5. Give Poiseuille’s radius dependence, and the reason capillaries do not therefore dominate resistance.
6. Compute alveolar ventilation from tidal volume, dead space, and frequency, and state what the alveolar gas equation needs as inputs.
7. Define the Bohr and Haldane effects so the names cannot be swapped, and write the chloride shift in one sentence.
8. Contrast inulin clearance with PAH clearance, and name the segment that both dilutes the urine and builds the medullary gradient.
9. Give the directions of pH, PCO2, and HCO3− in compensated respiratory acidosis and compensated metabolic acidosis.
10. In moderate exercise, state what happens to heart rate, stroke volume, total peripheral resistance, arterial PCO2, and insulin, and why the baroreflex does not slow the heart.
Selected sources #
These notes are an original teaching summary, not a transcript of any textbook.
- Hall JE, Hall ME. Guyton and Hall Textbook of Medical Physiology. Elsevier.
- Boron WF, Boulpaep EL. Medical Physiology. Elsevier.
- Sherwood L. Human Physiology: From Cells to Systems. Cengage.
- Schmidt-Nielsen K. Animal Physiology: Adaptation and Environment. Cambridge University Press.
- Cannon WB. Organization for physiological homeostasis. Physiological Reviews 9:399–431 (1929).
- Bayliss WM, Starling EH. The mechanism of pancreatic secretion. Journal of Physiology 28:325–353 (1902).
- Starling EH. On the absorption of fluids from the connective tissue spaces. Journal of Physiology 19:312–326 (1896).
- Bohr C, Hasselbalch K, Krogh A. Über einen in biologischer Beziehung wichtigen Einfluss, den die Kohlensäurespannung des Blutes auf dessen Sauerstoffbindung übt. Skandinavisches Archiv für Physiologie 16:402–412 (1904).
- Christiansen J, Douglas CG, Haldane JS. The absorption and dissociation of carbon dioxide by human blood. Journal of Physiology 48:244–271 (1914).
- Landsteiner K. Über Agglutinationserscheinungen normalen menschlichen Blutes. Wiener klinische Wochenschrift 14:1132–1134 (1901).
- de Bold AJ, Borenstein HB, Veress AT, Sonnenberg H. A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats. Life Sciences 28:89–94 (1981).
- Preston GM, Carroll TP, Guggino WB, Agre P. Appearance of water channels in Xenopus oocytes expressing red cell CHIP28 protein. Science 256:385–387 (1992).
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# Part C. Visual Figures & Scientific Diagrams Gallery
Comprehensive high-resolution visual reference repository for Animal & Human Physiology from the B10logy Visual Atlas.
An Annotated Of An Alveolus
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# Part C. Visual Figures & Scientific Diagrams Gallery
Essential high-resolution reference diagrams for Animal and Human Physiology from the B10logy Visual Atlas.
