DENT2052 Course Summary (Part C)

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Module VI Endocrinology PITUITARY GLAND The pituitary gland (or hypophysis) is a small endocrine gland located at the base of the brain just below the hypothalamus.

It contains two anatomically and functionally distinct lobes: o The posterior pituitary (or neurohypophysis) is simply an extension of the hypothalamus (almost indistinguishable from it), containing

These nerve terminals release just two hormones: vasopressin (ADH) which regulates water balance, and oxytocin which stimulates uterine contraction and milk ejection from the mammary glands during

o The anterior pituitary is much more complex than the posterior pituitary while the posterior pituitary which releases hormones synthesised by the hypothalamus, the anterior pituitary itself

2 Module VI Endocrinology PITUITARY GLAND The pituitary gland (or hypophysis) is a small endocrine gland located at the base of the brain just below the hypothalamus. It is connected to the hypothalamus by a thin connecting stalk. It contains two anatomically and functionally distinct lobes: o The posterior pituitary (or neurohypophysis) is simply an extension of the hypothalamus (almost indistinguishable from it), containing a dense collection of nerve terminals. These nerve terminals release just two hormones: vasopressin (ADH) which regulates water balance, and oxytocin which stimulates uterine contraction and milk ejection from the mammary glands during breastfeeding. o The anterior pituitary is much more complex than the posterior pituitary while the posterior pituitary which releases hormones synthesised by the hypothalamus, the anterior pituitary itself synthesises the hormones it releases into the blood. A collection of functionally distinct cells in the anterior pituitary each secrete different hormones (called tropic hormones): Somatotrophs secrete growth hormone (GH) (or somatotropin), the primary hormone responsible for regulating overall body growth. Lactotrophs secrete prolactin (PRL) (or mammotropin), which enhances breast development and lactation in females. Gonadotrophs secrete follicle stimulating hormone (FSH) which regulates gamete production, and luteinizing hormone (LH) which controls sex hormone secretion. Thyrotrophs secrete thyroid stimulating hormone (TSH) (or thyrotropin), which stimulates secretion of thyroid hormones and thyroid gland growth. Corticotrophs secrete adrenocorticotrophic stimulating hormone (ACTH) (or corticotropin), which stimulates cortisol secretion by the adrenal cortex. 2

o Each lobe is comprised of many spheres known as follicles.

3 THYROID GLAND SYNTHESIS The thyroid gland lies over the trachea just below the larynx. It consists of two lobes of endocrine tissue joined in the middle by a narrow portion called the isthmus this gives it a bow tie -like shape. o Each lobe is comprised of many spheres known as follicles. In a histological section, the follicles appear as rings, consisting of a single layer of outer follicular cells which enclose an inner lumen filled with colloid. This colloid is considered extracellular, because it is separate from follicular cells. It serves as an extracellular storage site for thyroid hormones. o The chief constituent of colloid is thyroglobulin (Tg), a complex protein extremely rich in the amino acid tyrosine (Tyr). o Between the follicles lie many capillaries which deliver blood to the follicular cells. o Another secretory cell type known as parafollicular cells (or C cells) lie in the interstitial spaces between the follicles. These cells secrete the peptide hormone calcitonin, which acts to reduce blood calcium levels (not related to the thyroid hormones). The follicular cells produce two iodine-containing hormones derived from tyrosine: thyroxine (T4) (or tetraiodothryonine) and tri-iodothyronine (T3). These two hormones are collectively referred to as thyroid hormones. The basic ingredients for thyroid hormone synthesis are tyrosine and iodine tyrosine is synthesised in sufficient amounts by the body, but iodine must be obtained from dietary intake. The following steps outline the synthesis and secretion of thyroid hormones: 1. Tg EXOCYTOSIS Thyroglobulin (Tg) produced in the follicular cells (by the ER and Golgi) is transported into the colloid via exocytosis. 2. TRAPPING Thyroid-stimulating hormone (TSH) (also known as thyrotropin) upregulates the activity of the Na + /I cotransporter (NIS) on the basolateral membrane (facing the interstitial fluid) of the follicular cell. This allows iodide (I ) to be carried into the follicular cell and trapped. 3. OXIDATION At the luminal membrane (facing the lumen) of the follicular cell, iodide is oxidised to its active form (iodine (I 0 )) by thyroperoxidase (TPO). 4. IODINE EXOCYTOSIS The active iodine then enters the colloid-filled lumen through a luminal channel (probably pendrin, an I /Cl transporter). 5. IODINATION TSH stimulates the iodine to attach to a tyrosine within the Tg molecule (known as tyrosal residues) in a process called iodination. This process is catalysed by TPO which originally oxidised iodide to iodine in step 3. a. The attachment of one iodine to tyrosine yields monoiodotyrosine (MIT). b. The attachment of two iodines to tyrosine yields di-iodotyrosine (DIT). 6. CONJUGATION TSH now stimulates a coupling process within the Tg molecule between the iodinated tyrosines to form the thyroid hormones T3 and T4 in a process called conjugation or oxidative condensation: a. The coupling of one MIT and one DIT yields T3. b. The coupling of two DITs yields T4. 3

PANCREAS The pancreas is an organ composed of both exocrine and endocrine tissues.

There are three types of cells in an islet of Langerhan: o The β cells synthesise and secrete insulin, and constitute 60% of the total islet mass.

o The δ cells (or D cells) synthesise and secrete somatostatin, constituting just 10% of the islet mass. Pancreatic somatostatin regulates insulin and glucagon via paracrine actions.

Blood always flows from the centre of the islet to the periphery.

In the rough endoplasmic reticulum, the leader sequence is removed and the molecule folds in a way that lines up cysteines so that disulfide bridges can form this creates proinsulin.

4 PANCREAS The pancreas is an organ composed of both exocrine and endocrine tissues. Between the exocrine cells are about a million clusters (or islands ) of endocrine cells known as the islets of Langerhans. There are three types of cells in an islet of Langerhan: o The β cells synthesise and secrete insulin, and constitute 60% of the total islet mass. o The α cells synthesise and secrete glucagon, constituting around 25% of the islet mass. Glucagon and other hormones (glucocorticoids, adrenaline) are glucogenic. o The δ cells (or D cells) synthesise and secrete somatostatin, constituting just 10% of the islet mass. Pancreatic somatostatin regulates insulin and glucagon via paracrine actions. o Most insulin, glucagon and somatostatin are in close proximity to vascular cells. Endocrine cells are aligned along the blood vessels in a random order. Blood always flows from the centre of the islet to the periphery. Synthesis of insulin begins at its biologically inactive precursor preproinsulin a peptide consisting of a leader sequence, an A chain, a B chain and a C-peptide. In the rough endoplasmic reticulum, the leader sequence is removed and the molecule folds in a way that lines up cysteines so that disulfide bridges can form this creates proinsulin. Proinsulin is then stored in secretory molecules. When secretion is stimulated (requires camp and Ca 2+ ), convertases cleave off the inactive C-peptide to release the active insulin. Secretion of insulin is regulated by many factors: o An increase in blood glucose concentration (the primary stimulus) o Elevated blood amino acid concentration (especially arginine and lysine) o Increased gastrointestinal hormones (such as CCK (cholecystekinin), GIP (gastric inhibitory peptide), gastrin, secretin) o Increased parasympathetic stimulation o Decreased sympathetic stimulation 4

Module VII Reproductive Physiology FEMALE REPRODUCTION In females, the reproductive organs (or gonads) consist of a pair of ovaries and a reproductive tract.

o The thick-walled, hollow uterus maintains the foetus during its development and expels it at the end of pregnancy. It consists of three layers: The endometrium is the inner layer of mucosa.

5 Module VII Reproductive Physiology FEMALE REPRODUCTION In females, the reproductive organs (or gonads) consist of a pair of ovaries and a reproductive tract. o The reproductive tract itself consists of two oviducts (also known as uterine or Fallopian tubes), which pick up ova on ovulation and serve as the site of fertilisation. o The thick-walled, hollow uterus maintains the foetus during its development and expels it at the end of pregnancy. It consists of three layers: The endometrium is the inner layer of mucosa. The cells of the endometrium secrete fluids and nutrients into the uterus itself thus it is very highly vascularised. The myometrium is the middle layer, composed of bundles of smooth muscle. It is responsible for contraction of the uterus to force the baby out during parturition. The perimetrium is the outermost serous layer of the uterus. o The vagina is a muscular, expandable tube connecting the uterus to the external environment. The vagina is connected to the uterus by a cervical canal, which serves as a pathway for sperm to the site of fertilisation. Oogenesis is the process of generating the female gamete the ovum. o Before birth, the undifferentiated primordial germ cell is the oogonium (around 6 7 million). o During the last part of foetal life, the oogonia begin the first meiotic division, but do not complete it (they contain the diploid number of 46 replicated chromosomes, but the cells do not separate) this is known as arrested meiotic division. At this stage they are known as primary oocytes (2 million). 5

The adjacent diagram is a more detailed overview of steroid synthesis in the follicles: o Cholesterol from the blood enters the theca.

o The testosterone then enters the granulosa, where FSH and aromatase stimulate its conversion to oestradiol. o Oestradiol then diffuses to the blood and follicular fluid.

The ovarian cycle is commonly divided into four phases: o Before the follicular phase (at the beginning of menstruation), the endometrium of the uterus starts to slough off (due to the

o FOLLICULAR PHASE HORMONES The follicle secretes oestrogen under the influence of FSH, LH and oestrogen itself.

6 The adjacent diagram is a more detailed overview of steroid synthesis in the follicles: o Cholesterol from the blood enters the theca. Under the action of LH, cholesterol undergoes a series of reactions and is transformed into testosterone. o The testosterone then enters the granulosa, where FSH and aromatase stimulate its conversion to oestradiol. o Oestradiol then diffuses to the blood and follicular fluid. The menstrual cycle (or ovarian cycle) refers to the reproductive cycle in primates. Changes in the hormone levels, ovary, and uterus must be considered. The ovarian cycle is commonly divided into four phases: o Before the follicular phase (at the beginning of menstruation), the endometrium of the uterus starts to slough off (due to the low levels of oestrogen and progesterone), dramatically reducing its thickness. This is known as the menstrual phase of the uterine cycle. o FOLLICULAR PHASE HORMONES The follicle secretes oestrogen under the influence of FSH, LH and oestrogen itself. OVARY There is sufficient FSH and oestrogen to induce the follicular development of around 6 12 follicles. A dominant follicle outgrows the subdominant follicles via the effect of inhibin. Inhibin also inhibits secretion of FSH, which declines (while LH keeps rising). The dominant follicle will mature to a Graafian follicle. UTERUS Oestrogen alone (without FSH) also induces regrowth of the endometrium of the uterus this is known as the proliferative phase of the uterine cycle. 6

MALE REPRODUCTION The male reproductive organ can be divided into two systems: o The duct system provides a passage for mature sperm to reach the external environment.

Mature sperm passes from these tubules into the epididymis (the start of the male reproductive tract).

o The accessory glands are responsible for adding fluids to the ejaculate. They include the seminal vesicles, the prostate gland and the bulbourethral glands.

As females lack the SRY gene, the gonadal cells never receive a signal for testes formation, and they develop into the ovaries instead by default.

7 MALE REPRODUCTION The male reproductive organ can be divided into two systems: o The duct system provides a passage for mature sperm to reach the external environment. It begins at the male gonads a pair of testes. 80% of each testis consists of a mass of highly coiled seminiferous tubules this is the site of spermatogenesis (sperm production). Mature sperm passes from these tubules into the epididymis (the start of the male reproductive tract). Sperm then travels up the ductus deferens, down through the ejaculatory duct and into the urethra a canal that runs the length of the penis and empties to the exterior. o The accessory glands are responsible for adding fluids to the ejaculate. They include the seminal vesicles, the prostate gland and the bulbourethral glands. Development of the testes is dependent on the SRY gene (sexdetermining region Y) on the Y chromosome. As females lack the SRY gene, the gonadal cells never receive a signal for testes formation, and they develop into the ovaries instead by default. Once developed, the testes are responsible for three major actions: o Production of sperm and fluid (semen/ejaculate) o Synthesis and secretion of hormones (androgens, oestradiol, inhibin) o Isolation of spermatogenesis via the blood-testis barrier (such that damaging substances in the blood do not reach the sperm). The adjacent diagram represents a cross-section of a seminiferous tubule. Each tubule contains many different cell-types: o Just as the undifferentiated primordial female germ cell was the oogonium, the undifferentiated male germ cell is the spermatogonium. Differentiation increases with closer proximity to the lumen of the tubule, and in the lumen are the fully mature differentiated spermatozoa (colloquially sperm ), recognisable by their tails. o The Sertoli cells (or nurse cells) are epithelial cells lying side by side, forming a ring that extends from the outer basal lamina of the tubule to the lumen. Adjacent Sertoli cells are joined by tight junctions. Developing sperm cells are tucked between adjacent Sertoli cells, with spermatogonia lying at the outer perimeter of the tubule, outside the tight junction. o Leydig cells (or interstitial cells) lie in the connective tissue between the seminiferous tubules. 7

Chapter 22 The Reproductive System (I)

Chapter 22 The Reproductive System (I) An Overview of Reproductive Physiology o The Male Reproductive System o The Female Reproductive System 22.1 Reproductive System Overview Reproductive system = all