#13359 - Pituatary Gland Essay - Organisation of the Body

Describe the anatomical organisation of the pituitary gland. Explain the control and actions of ACTH and the consequences if control is dysregulated.

The organisation of the pituitary gland

The pituitary gland is a pea sized endocrine gland that sits in the pocket of the sphenoid bone and is attached inferiorly to the median eminence of the hypothalamus of the brain via a pituitary stalk, also known as the ifundibulum. It consists of an anterior lobe (adenohypophysis) which consititutes for 2/3^rd of the volume and a posterior lobe (neurohypophysis) which forms the remaining 1/3^rd. The formation of the pituitary gland begins in the 5^th week of embryonic development. The adenohypophysis is formed by an upward invagination of the oropharyngeal ectoderm which forms the Rathke’s pouch and this later constricts and is pinched of from the ectoderm. Whereas the pituitary stalk (ifundibulum) and the neurohypophysis are formed from the downward extension of the neural ectoderm in the diencephalon region. The site where the ectoderm of both the anterior and posterior lobe meet forms the intermediate lobe but is anatomically considered to be part of the anterior lobe. The posterior lobe of the pituitary gland is supplied by the internal carotid artery and its branches form a capillary plexus at the base of the hypothalamus. This plexus is continuous with the hypothalamo-hypophysial portal veins which travels down the pituitary stalk into the anterior lobe. This portal vein is a vital connection and allows the neuroendocrine cells of the hypothalamus to control secretions of the hypothalamus.

The posterior lobe is continuous with the hypothalamus and is formed by nerve terminals of hypothalamic magnocellular neurosecretory neurons, which are large neuroendocrine cells that secrete oxytyocin and vasopressin on electrical excitation. The hormones secreted by the posterior lobe are synthesised in the hypothalamus which are then packaged into vesicles and are transported down the axons. On nervous stimulation the hormones are released into the systemic veins by excocytosis. The terminals are surrounded by pituicytes.

The anterior lobe is made up of a collection of endocrine cells that can be identified through electron microscopy and also by immunocytochemistry which classes these secretory cells according to the specific protein they secrete. The composition of the secretory cells classified on the type of hormone they release is listed below:

The anterior lobe is under chemical control unlike the posterior lobe which is under electrical control. The neurohormones secreted by the neurons of the hypothalamus into the capillary plexus formed by a branch of the internal carotid artery, controls the secretion of hormones in the anterior lobe of the pituitary gland even though the two structures are not anatomically connected. The neurohormones enter into enter the anterior lobe of the pituitary gland via the hypothalamo-hypophysial portal veins and from here it diffuses out and acts on endocrine cells The neurohormones released by the hypothalamus have mostly stimulatory effect on the endocrine cells and triggers the release of hormones into the jugular veins where they are transported to their target tissues. The key evidence which showed that the anterior pituitary was functionally linked to the hypothalamus was shown Geoffrey Harris. When rabbits were injected with Indian ink there was an abundance in the pituitary stalk showing there was a vascular connection between the anterior pituitary and the hypothalamus. When the pituitary stalk was removed all the target endocrine glands shrunk but when reconnected the glands regrew in size. The release of hormones from the endocrine cells is also controlled by systemic hormones which exhibit a feedback control and also by paracrine interactions within the anterior lobe

The actions of ACTH

Adenocorticotrophic hormone is released by the corticotroph cells which are endocrine cells found in the anterior lobe. The release of this hormone is triggered by corticotrophin releasing hormone which is secreted from the neuroendocrine cells of the hypothalamus. Once the hormones are secreted by the hypothalamus they are taken up by leaky capillaries, which are not part of the blood brain barrier and are then transported to the anterior pituitary via the pituitary portal veins. The corticotrophin releasing hormone then binds to G-protein coupled receptors of the cell membranes of corticotroph cells and this leads to the alpha subunit of the Gs proteins activating adenylate cyclase. The enzyme leads to an increase in the concentration of the second messenger molecule cyclic AMP which inturn activates protein kinase A. The protein kinase A phosphorylates L type calcium channels leading to a greater influx of calcium ions. The increase in intracellular calcium concentration leads to the excocytosis of ACTH into the systemic veins

Adrenocorticotrophin hormone is a 39 amino acid peptide hormone that is formed from the cleavage of the prohormone pro-opiomelanocortin which is also a precursor for a wide variety of other peptide hormones such as B lipotropin, endorphin and melanocyte-stimulating hormones. The melanocyte stimulating hormone stimulates the pigmentation of the skin through its actions on melanocytes. The majority of the peptide hormones are glycosylated. The amount of adrenocorticotrophin hormone synthesised depends on corticotrophin releasing hormones as continued stimulation of the corticotroph receptors leads to increased synthesis. Arginine vasopressine hormone synthesised in the posterior lobe also promotes the secretion of adrenocorticotropin hormone.

Once the adrenocorticotrophin hormone is released into systemic circulation it binds to MCR2 receptors on secreting cells which are found in the fasiculate and reticularis layers of the adrenal cortex. The activation of the MCR2 receptor triggers the synthesis and secretion of the steroid hormone, cortisol which is a type of glucocorticoid that is responsible for regulation of glucose metabolism. The binding of ACTH leads to an increase in cyclic AMP which leads to activation of protein kinase A. The immediate response to ACTH binding is phosphorylation of the cholesterol side chain cleavage enzyme and this leads to increased conversion of cholesterol into pregnenolone which is the rate limiting step in the synthesis of cortisol. Over a longer period of time the binding of ACTH leads to the increased synthesis of various enzymes such as P-450 enzymes, which are needed in cortisol synthesis, LDL receptors, which are required for the uptake of cholesterol from blood, and HMG-CoA reductase which catalyses the rate limiting step of cholesterol synthesis. It also has a minor effect on aldosterone secretion by binding to glomerulosa cells of the adrenal cortex. In these cell the ACTH hormones triggers the synthesis of deoxycorticosterone which is a precursor of aldosterone. Aldesterone is a type of minerlocorticoid whose main function is to act on distal tubes and collecting ducts of the kidney and increase the reabsorption of ions and water. This leads to an increase in blood pressure. Finally a secondary effect of the ACTH is that is stimulates the growth of the adrenal cortex. This was shown as an abscence of ACTH leads to the atrophy of the fasciculate and reticularis layers of the adrenal cortex.

Control of ACTH secretion

There are two ways in which the secretion of ACTH from the anterior pituitary gland is controlled. The first way is through the neurohormone, corticotrophin releasing hormone (CRH). The effect of CRH can be seen when measuring the concentration of ACTH in the systemic circulation. It is seen that the concentration is very high early in the morning, around 7.00 and diminishes throughout the day and by midnight is recorded at very low levels. This shows that the pituitary secretes ACTH with a...