The pituitary gland is situated beneath the hypothalamus of the brain, in a depression, the ‘pituitary fossa’, of the skull. The pituitary comprises anterior, intermediate and posterior lobes.
Developmentof the pituitary gland (or hypophysis)
Rathke's pouch grows up from oropharyngeal ectoderm (roof of the mouth) to form the anterior pituitary. The infundibular process grows down from the forebrain vesicle to form the posterior pituitary. The portion of Rathke’s pouch in contact with the posterior pituitary forms the intermediate lobe. This lobe remains intact in some species but in humans its cells become interspersed with those of the anterior pituitary.
posterior pituitary: blood supply direct from internal carotid artery.
hypothalamus: branches direct from internal carotid artery. These form a capillary plexus in the base of the hypothalamus that gives rise to hypothalamo-hypophysial portal veins which run down the pituitary stalk to the anterior pituitary.
anterior pituitary: blood supply is from the hypothalamo-hypophysial portal veins.
The anterior pituitary consists of numerous individual endocrine cells. There are distinct cell types which produce and secrete the various hormones termed thyrotrophs, corticotrophs, gonadotrophs, lactotrophs and somatotrophs. Glial like folliculostellate cells surround and support the endocrine cells. The different cell types can be identified by immunocytochemistry and by their structural appearance under the electron microscope.
The anterior pituitary is regulated by
a) neurohormones from the hypothalamus – ‘central control’. Overall hypothalamic control is stimulatory for all anterior pituitary hormones except PRL (inhibitory). The pulsatile release of hypothalamic releasing factors stimulate pulses of anterior pituitary hormones.
b) systemic hormones – ‘feedback control’, mainly negative, by target hormones.
c) Paracrine interactions in the anterior pituitary.
The posterior pituitary is formed by the axons and terminals of magnocellular neurosecretory neurons originating in the hypothalamus. Pituicytes (a type of glial supporting cell) surround and support the terminals. The posterior pituitary hormones are synthesized in the hypothalamus, packed into granules, transported down the axons and released by exocytosis into the systemic veins draining the neurohypophysis.
The posterior pituitary releases the peptide hormones vasopressin and oxytocin, produced from prohormones.
Release of hormones from the posterior pituitary is controlled entirely in the hypothalamus.
HORMONES OF THE ANTERIOR PITUITARY Thyroid Stimulating Hormone =TSH, or thyrotrophin. Secreted by thyrotroph cells.
Chemical nature: glycoprotein hormone made of alpha and beta subunits; the beta subunit is specific to TSH, the alpha subunit is shared with LH and FSH.
Receptors:G protein coupled to cAMP, on thyroid gland follicular cells.
Actions: TSH acts in the thyroid: it stimulates thyroid hormone (T3 and T4 – see Thyroid lecture week 4) production; increases iodine uptake by the thyroid (required for thyroid hormone production) and stimulates thyroid growth.
Control: TSH release is stimulated by thyrotrophin releasing hormone (TRH) from the hypothalamus. Secretion of TRH is stimulated by cold and by stress via the CNS. TSH is released in pulses with a diurnal rhythm.
Systemic control of TSH release: inhibited by T3 & T4 negative feedback.
Dysfunction: TSH disorders are very rare.
Adreno Cortico Trophic Hormone =ACTH or corticotrophin. Secreted by corticotroph cells.
Chemical nature: polypeptide hormone cleaved from the prohormone, ProOpioMelanoCortin (POMC).
Receptors: G protein coupled to cAMP, in adrenal cortex.
Actions: Stimulates production and therefore secretion of cortisol (glucocorticoid steroid hormone) from the cortex of the adrenal gland (see Adrenal lecture week 5). ACTH produces some increase in adrenal sex steroids also and stimulates growth of the adrenal cortex. Melanocyte-Stimulating Hormones (MSH) is also cleaved from POMC and is released by corticotrophs. MSH stimulates pigmentation of skin via actions on melanocytes.
Control: Secretion of ACTH is increased by stress. Secretion is pulsatile with a diurnal rhythm (high at 7.00am, low at midnight). Release of ACTH is stimulated by corticotrophin releasing hormone (CRH) from the hypothalamus.
Systemic control of ACTH release: inhibited by glucocorticoid negative feedback.
Dysfunction: Excess ACTH from corticotrophinoma pituitary tumours causes excess glucocorticoid secretion - Cushing's disease; deficiency of ACTH causes glucocorticoid deficiency - Addison's disease. Nelson's syndrome - increased pigmentation via excess MSH secretion due to lack of negative feedback actions of cortisol on POMC expression after adrenal cortex surgery.
Chemical nature: glycoprotein hormones made up of an alpha and a beta subunit; the alpha subunit is common with that in TSH, the beta subunitss are specific to LH and FSH.
Receptors: both are G protein coupled to cAMP in ovary and testes.
Actions: Female: LH and FSH control growth and development of follicles; ovulation; synthesis of sex steroids by the ovary; growth and secretion of the sex steroid progesterone by the corpus luteum. Male: LH controls testosterone production by the Leydig cells; FSH stimulates the Sertoli cells and sperm production – see Trinity Term Reproduction lectures.
Control: Hypothalamic: LH and FSH release is stimulated by hourly pulses of gonadotrophin releasing hormone (GnRH) during reproductive life.
Systemic: inhibited by sex steroid oestrogen by negative feedback; however switch to 'positive feedback' triggers LH surge at ovulation. Cyclical variations in LH and
FSH in menstrual cycle. In males LH release is inhibited by negative feedback from testosterone; ovarian peptides (inhibin & follistatin) inhibit FSH.
Dysfunction: Deficiencies of LH and FSH or receptor dysfunction as a result of genetic mutations causes infertility in adult life and lack of sexual maturation in children. Excess LH and FSH secretion (nearly always due to inappropriate hypothalamic GnRH secretion) or receptor overactivity due to an activating mutation causes precocious puberty.
Prolactin= PRL, mammotrophin. Secreted by lactotroph cells.
Chemical nature: protein.
Receptor: single-transmembrane tyrosine kinase, in breast.
Actions: Principal role in preparation for lactation. There is a marked increase in the number of PRL cells in pregnancy, to the extent that the pituitary size nearly doubles. PRL stimulates the development and growth of secretory alveoli in the breast and milk production. PRL also inhibits the reproductive system at the level of the gonads and pituitary (causes ‘lactational amenorrhoea’ in women after delivery of baby- see Trinity Term reproduction lectures).
Control: Secretion of PRL is increased by suckling.
PRL is the only pituitary hormone whose principal control is inhibition by the hypothalamus. PRL release is inhibited by dopamine from the hypothalamus, PRL synthesis is stimulated by circulating oestrogen.
Dysfunction: Hypersecretion of PRL can occur from PRL-secreting tumours in the pituitary gland termed ‘prolactinomas’; causes galactorrhoea, infertility and impotence. Drugs that are dopamine agonists e.g. bromocryptine are used to suppress PRL release from tumours and are also used to suppress lactation in women.
Growth hormone = GH or somatotrophin. Secreted by somatotroph cells.
Chemical nature: protein.
Receptor: single-transmembrane tyrosine kinase.
Actions: Stimulates long bone and soft tissue growth, both via stimulating the release of IGFs (insulin-like growth factors) from the liver and by direct actions. It is essential for growth after 2 years postnatal but only promotes growth if sufficient nutrition is available. GH also exerts complex actions on metabolism (amino acid, fatty acid, glucose). GH has insulin-like effects to promote amino acid uptake by liver and muscle and therefore promotes protein synthesis. However, if GH is chronically increased it has anti-insulin effects. It is one of the hormones that switches metabolism away from glucose use and toward increased oxidation of fat (e.g. in starvation).
Control: GH is secreted in pulses about every 4h, and on entering deep sleep.
Secretion is increased via the hypothalamus by hypoglycaemia, stress and exercise.
Hypothalamic factors that regulate GH release are growth hormone releasing hormone (GHRH) which stimulates and somatostatin which inhibits GH release.
Systemic control is via negative feedback by GH at the hypothalamus.
Dysfunction: GH insufficiency causes short stature (dwarfism); GH excess causes gigantism in children, acromegaly in adults.
Receptors: acts on V2 receptors in kidney, G protein coupled to cAMP and V1 (PLC-coupled) receptors in vasculature.
Actions: increases water reabsorption by acting in collecting ducts of kidney (V2) and vascular pressor effects constricting peripheral arterioles and veins (V1).
Control: osmotic - sensitive to 1% increase from normal plasma OP - 285mOsm. This is sensed by hypothalamic osmoreceptors. These are also sensitive to decreases in blood volume or pressure.
Dysfunction:diabetes insipidus (hypothalamic and renal types) due, respectively to lack of ADH production and action.
Chemical nature: peptide of 9 amino acids.
Receptors: acts on membrane G protein coupled receptors coupled to PLC in breast and uterine muscle.
Actions: causes contraction of uterine myometrium in childbirth and causes contraction of breast myoepithelium to eject milk.
Control: stretch of cervix/vagina during parturition - the Ferguson reflex.