Q.1 Describe the structure and function of pituitary gland. (2005)
Related Questions -
Q. Describe the functions of hormones secreted by anterior pituitary gland. (2019)
Q. Enumerate the hormones of pituitary gland and describe their functions. (2012)
Q. Describe these structure and function of thyroid gland. (2009, 14)
Q. Write short note on Pituitary gland. (2013)
Q. Elaborate the structure and function of pituitary gland. (2015)
Ans.
ANATOMY: -
· The hypothalamus consists of nervous tissue lying inferior to the two lobes of the thalamus. The pituitary gland, or hypophysis, is found at the base of the brain below the hypothalamus and the two structures are connected via the infundibulum, or pituitary stalk, which carries both axons and blood vessels.
· The pituitary gland is about 1- 1.5 cm in diameter and weighs approximately 0.5g although it tends to weigh approximately 20% more in women and may increase by 10% during pregnancy. It sits in the sella turcica which is a depression of the sphenoid bone at the base of the skull and lies behind the sphenoid sinus.
· The top of the sella turcica is covered by a diaphragm, which has a foramen in the centre through which the infundibulum passes.
· Superior to the diaphragm is the optic chiasm.
· The pituitary gland can be divided into two functionally and embryologically distinct parts. These are the anterior pituitary, or adenohypophysis, and the posterior pituitary, or neurohypophysis.
· The anterior pituitary makes up 75% of the total weight of the pituitary. The pars distalis forms the major part of the gland. The pars intermedia is rudimentary in man. The pars tuberalis runs up the pituitary stalk.
· The posterior pituitary is made up of neuronal processes and glia as an extension of the hypothalamus and its major part is the pars distalis, which lies behind the anterior pituiary in the sella turcica.
Development: -
The pituitary gland is formed as a result of two separate developmental processes giving the anterior and posterior lobes.
· The posterior pituitary develops as an extension of the hypothalamus itself. The infundibulum is formed from the neuroectoderm of the floor of the third ventricle and develops to form the posterior pituitary. The median eminance is also formed from neuroectoderm.
· The anterior pituitary is derived from oral epithelium from the roof of the mouth cavity, which migrates upwards towards the neural tube. This outgrowth is known as Rathke’s pouch. It detaches itself by the 6th week of development although detachment is not always complete and may cause problems such as craniopharyngioma.
· The hypothalamo-pituitary axis is a functional unit by mid gestation.
Histology: -
· The endocrine cells of the anterior pituitary have traditionally been classified according to the pattern of staining giving acidophils, which stain with acidic dyes, basophils, which stain with basic dyes, and chromophobes, which have only pale staining.
· It is now possible to differentiate between the different hormone producing cells and divide the cells into 5 types with varying distribution within the gland.
· Somatotrophs secrete growth hormone (GH), are distributed laterally and make up 50% of hormone secreting cells.
· Thyrotrophs secrete thyrotropin (TSH), are concentrated laterally and make up 10% of cells.
· Gonadotrophs secrete luteinizing hormone (LH) and follicle stimulating hormone (FSH), are randomly distributed and make up 10% of cells. These cell types are distinguishable using immunohistochemical staining using antibodies to each hormone type.
· Corticotrophs secrete adrenocorticotrophic hormone (ACTH), b-lipotrophin, a -melanocyte stimulating hormone and b-endorphin, are found in the median portion and make up 15-20% of cells.
· Lactotrophs secrete prolactin, are randomly distributed and make up 25% of cells. The number of these cells increases in response to increased oestrogen in pregnancy and lactation.
Anterior Pituttary Hormones: -
There are 6 major hormones produced by the anterior pituitary, which can be grouped according to structure.
Luteinizing hormone, follicle stimulating hormone and thyroid stimulating hormone
These are glycoproteins with 2 subunits - a and b. They all have 204 amino acids. The a subunit is common to all these hormones in one species. The b subunit gives specificity of binding to receptors and so site of action. The carbohydrate portion of the b-subunit affects specificity and half-life.
Growth Hormone and Prolactin: -
These two hormones belong to a family of polypeptide hormones. They share elements of their structure and differ only by 8 amino acids, GH having 191 amino acids and prolactin having 199.
Adrenocorticotropin Hormone: -
This is a polypeptide derived from the pro-opiomelanocortin (POMC) precursor molecule, which also gives rise to products such as melanocyte stimulating hormone, lipotrophic hormone and b-endorphin. It has 39 amino acids.
Thyroid Stimulating Hormone or Thyrotrophin: -
· TSH is released from the anterior pituitary gland in response to thyroid releasing hormone from the hypothalamus and causes the synthesis and secretion of triiodothyronine (T3) and thyroxine (T4) by the thyroid gland.
· This is acheived by stimulation of the thyroid follicular cells by binding of TSH to the receptor on the basal surface of the cell and activation of adenylate cyclase.
· This leads to iodide uptake. T3 and T4 exert negative feedback on both the pituitary production of TSH and the hypothalamic production of TRH.
· Other factors affecting release of TRH from the hypothalamus incluse blood levels glucose and the body’s metabolic rate.
· Somatostatin inhibits TSH secretion and oestrogen has been shown, in rats, to reverse the negative feedback affect of T3 and T4 on the TSH response to TRH.
Problems at the level of the hypothalamo-pituitary axis can cause deficiency of TSH resulting in secondary hypothyroidism which is normally less severe than that caused by disease of the thyroid gland itself. Congenital problems such as pituitary hypoplasia of aplasia may affect any of the pituitary hormones. There may be a loss of midline structures as in septo-optic dysplasia, which also causes loss of optic nerves.
The effects are due to lack of production of thyroid hormones. Treatment is by administration of oral thyroxine
Effects of TSH Deficiency: -
Hyperthroidism has the opposite symptoms to hypothyroidism including increased oxygen consumption, increased metabolism, weight loss, heat intolerance, sweating, insomnia and nervousness. The most common form is Graves’ disease, an autoimmune condition in which thyroid stimulating immunoglobulins exist that mimic the action of TSH but with no normal feedback control. This results in continual production of thyroid hormones and an enlarged thyroid gland. Treatment is with anti-thyroid drugs or by thryoid gland surgery. It is rare to see overproduction of TSH due to a pituitary adenoma.
Gonadotrophins-Luteinizing Hormone and Follicle Stimulating Hormone: -
· The hypothalamo-pituitary-gonadal axis is different in males and females.
· In females GnRH is secreted from the hypothalamus in a cyclical way leading to a cyclical secretion of LH and FSH from the pituitary, which maintains the menstrual cycle.
· LH acts on the ovarian follicle and it induces ovulation and maintains the corpus luteum.
· FSH causes development of the ovarian follicle and stimulates secretion of oestradiol and progesterone.
· The sex steroids feed back to inhibit release of GnRH and therefore LH and FSH. At sustained high levels however, oestradiol causes a sharp increase in LH secretion linked to ovulation. This is an example of positive feedback.
· In males GnRH causes the release of LH and FSH from the anterior pituitary, as in females.
· LH acts on the Leydig cells of the testes to produce testosterone.
· FSH acts on the Sertoli cells of the testes to maintain spermatogenesis as well as production of sex-hormone binding globulin.
In males and females FSH stimulates the production of inhibin, which has a negative feedback effect on the hypothalamus and pituitary.
Insufficient GnRH causes a fall in gonadotrophin production, which leads to amenorrhoea, due to lack of ovulation, in women and impotence and infertility in men. This is sometimes seen when nutrient intake is too low, as in anorexia nervosa, or when excessive exercise is undertaken. It may also be due to a prolactin secreting tumour because prolactin has effects on the hypothalamo-pituitary-gonadal axis. The problems caused by lack of GnRH may be treated by administration of GnRH, gonadotrophins such as recombinant FSH, or sex steroids.
Growth Hormone: -
· Growth hormone release from the anterior pituitary is under the control of two hypothalamic hormones.
· GHRH acts to stimulate release of GH while somatostatin acts to inhibit release of GH.
· GH exerts its effects directly and also indirectly through insulin-like growth factors (IGFs) 1 and 2. The effects include promotion of growth of bone, soft tissue and viscera as well as having affects on protein synthesis, lipolysis and glucose transport and metabolism. IGF1 provides negative feedback to the pituitary and hypothalamus.
Other factors affecting GHRH and somatostatin secretion include sleep, exercise, stress and blood glucose levels. Oestradiol also acts to increase sensitivity of tissues to GH.
A GH secreting tumour may be present in the pituitary gland leading to excessive height due to extra GH during childhood. Excessive production of GH in adulthood,after the growing ends of the bones have fused, leads to the condition of acromegaly and this can be seen as enlarged feet, hands and jaw caused by thickening of the bones as well as thickening of the soft tissue.
Insulin resistance also develops, due to downregulation of the insulin receptors caused by increased insulin production in response to increase glucose concentrations. This gives the symptoms of diabetes mellitus. Treatment of acromegaly is usually surgery to remove the tumour. The dopamine agonist bromocriptone is sometimes administered and somatostatin analogues may also be used.
Hyposecretion if GH in childhood leads to pituitary dwarfism and a characteristic fat distribution concentrated around the face and abdomen caused by a loss of metabolic function. This may be due to a number of reasons, for example irradiation of the hypothalamo-pituitary area, surgery of the pituitary gland or trauma severing the link between hypothalamus and pituitary gland, which result in lack of hypothalamic or pituitary hormone secretion. The syndrome of hypopituitarism and the importance of GH in adults has only recently been recognised. Symptoms of lack of GH include increased abdominal adiposity, reduced strength and exercise capacity, reduced bone density, elevated cholesterol and impaired psychological well-being. GH deficiency in both adults and children can be treated successfully using recombinant human GH.
Prolactin: -
PRL acts to initiate and maintain milk secretion by the mammary glands. It works with other hormones such as oxytocin, which actually causes milk ejection, and oestradiol, progesterone, glucocorticoids, GH, thyroxine and insulin, which prepare the mammary gland for milk production.
Other functions are unclear but experimental animals have been shown to produce PRL in response to stress. PRL may also play a part in fertility and maternal behaviour.
PRL secretion is under inhibitory control of dopamine. This means that if the link between the hypothalamus and pituitary is severed PRL secretion increases, unlike all other pituitary hormones, where production would decrease without stimulatory control of the hypothalamus.
TSH has a stimulatory affect on PRL secretion. Oestradiol increases PRL production and levels of PRL rise during pregnancy and remain high during lactation.
PRL secreting tumours are a very common type of pituitary tumour. The high levels of PRL lead to loss of reproductive function and inappropriate milk production (galactorrhoea) in males and females although male symptoms are often less obvious. Treatment is with the dopamine agonist bromocriptine. Undersecretion of PRL is very rare and does not have any clinical symptoms.
Adrenocorticotrophic Hormone: -
ACTH is released in a pulsatile fashion from the pituitary following a circadian rhythm, peaking in the morning and then declining. It is released under control of hypothalamic CRH.
The release of CRH can be affected by external influences such as stress. CRH action is potentiated by petides such as vasopressin.
ACTH controls the production of glucocorticoids by the adrenal cortex, stimulating the conversion of cholesterol to pregnenolone - a precursor of cortisol. Cortisol feeds back to inhibit both the hypothalamus and pituitary gland.
Oversecretion of ACTH leads to symptoms known as Cushing syndrome. When this is a result of a feedback abnormality it is Cushing disease and is caused by ACTH and CRH secretion being suppressed at abnormally high levels of circulating cortisol. This results in an ACTH secreting pituitary tumour due to overstimulation of the corticotrophs and excess cortisol secretion secondary to this. Excess cortisol secretion may also be caused by a CRH secreting tumour Symptoms of excess cortisol include central obesity, thinning of the skin, bruising, glucose intolerance, susceptibility to infection, muscle wasting and thin bones. Hyperpigmentation of the skin may occur due to the associoated secretion of a-MSH with ACTH. When excess ACTH drives excess cortisol production adrenal androgens are also oversecreted leading to symptoms of androgen excess. Treatment is surgery to remove the tumour. Undersecretion of ACTH leads to problems of glucocorticoid deficiency, such as hypoglycaemia, and androgen deficiency, such as lack of pubic hair and libido in females. This can be treated by administering hydrocortisone.
Posterior Pituttary Hormones: -
The hormones produced by the posterior pituitary gland are oxytocin and vasopressin, which is also known an arginine vasopressin (AVP) or antidiuretic hormone (ADH). These are both peptides with similar structures and made up of 9 amino acids. Their properties are determined by the residue at position 8.
Oxytocin: -
Oxytocin secretion occurs in response to nervous stimulation of the hypothalamus. This hormone causes contraction of the smooth muscle of the uterus and also of the myoepithelial cells lining the duct of the mammary gland. Although some oxytocin is found in males, its function is unclear.
Release of oxytocin is under positive feedback control. Stimulation of mechanoreceptors in the uterus and vagina during parturition cause a rise in oxytocin levels up to a maximum until the stimulus is no longer present and the action of the hormone is no longer needed. The nipple also sends nervous impulses to the hypothalamus upon suckling, leading to contraction of the myoepithelial cells and expulsion of milk under positive feedback control.
Oestradiol potentiates the uterus to oxytocin and progesterone blocks it. Oxytocin also acts with AVP to promote sodium excretion.
There are no known disorders of oxytocin secretion.
Vasopressin: -
· AVP acts primarily on the kidneys at V2 receptors to aid reabsorption of water by affecting the water permeability of the collecting duct of the kidney.
· At high concentrations it also causes constriction of the arterioles through its action at the V1 receptors leading to an increase in blood pressure.
· Osmoreceptors in the hypothalamus detect an increase in osmotic pressure in the blood. As well as producing the sensation of thirst in order to cause increased water intake, the hypothalamus causes the release of AVP, which acts to retain water and reduce plasma osmolality.
AVP is under negative feedback control. A fall in blood volume stimulates release of AVP. Also, a fall in the arterial partial pressure of oxygen and a rise in partial pressure of carbon dioxide stimulate AVP release. Secretion is also affected by the angiotensin II, adrenaline, cortisol and sex steroids. At the level of the hypothalamus, pain, trauma, nausea and vomiting, and a rise in external temperature increase AVP secretion, and psycological and emotional stimuli also affect release.
Overproduction of AVP can occur due to brain trauma. It leads to water retention, serum hypo-osmolality, hyponatraemia and high urine osmolality.These effects cause symptoms of headache, apathy, nausea and vomiting, impaired conciousness and can be fatal in extreme cases.
Underproduction of AVP results in the condtion of diabetes insipidus, which is neurogenic in origin (rather than due to failure of the kidneys to respond to AVP) and can result from a pituitary tumour, head traumas or surgery which damages the pituitary gland and hypothalamus.Sometimes it is due to autoimmune destruction of the AVP neurons. Clinical signs are excretion of large volumes of urine leading to dehydration and thirst, as well as increased plasma osmolality. The water deprivation test is often used as a diagnostic aid - patients are unable to concentrate their urine and when deprived of water will continue to pass dilute urine of low osmolality while plasma osmolality rises. Treatment of this condition is with analogues of AVP such as desamino D-arginine administered subcutaneously or by nasal spray.