#13341 - Endocrine Pituitary Gland - Organisation of the Body

Pituitary Gland –MASTER GLAND!!!!

Organisation of the pituitary gland

-pituitary gland sits below the hypothalamus of the brain in a midline fossa, pituitary fossa of the sphenoid bone

-it is connected to the median eminence of hypothalamus by a pituitary stalk- ifundibulum

-it is surrounded by skull so the if the gland enlargens there is no extra space so there are severe headaches.

-functionally, the gland is divided into two lobes- anterior lobe is 2/3 volume of the gland and posterior lobe is one third- both have different embryological orgins and control mechanisms

Development of the pituitary gland

- the anterior lobe (adenohypophysis) develops from an upward invagination, Rathke’s pouch, of the oropharyngeal ectoderm (roof of the mouth)- the rathke’s pouch constricts and is pinched off from the ectoderm.

-the posterior lobe (neurohypophysis) develops from the ifundibulum which is a downward extension of the neural ectoderm in the forebrain region.

-the portion of the rathke’s pouch in contact with the posterior pituitary forms the intermediate lobe. In humans the intermediate lobe becomes interspersed with those of the anterior pituitary.

anterior lobe (adenohypophysis)-

-collection of endocrine cells- types of endocrine cells can be identified through electron microscopy and by immunocytochemistry which classes cells depending on the specific protein they secrete

50% of secretory cells in the anterior lobe are somatotrophs- synthesise somatotrophin/GH

-Electron microscopy: the somatotrophs are packed with granules of moderate size

25% are lactotrophs- prolactin

10% are corticotrophs- ACTH

-sparse secretory granules located at the extreme periphery of a cell

15% are gonadotrophs- LH and FSH

-large cells with granules of various size

5% are thyrotrophs-TSH

-smaller granules

-surrounding the endocrine cells are gilial like cells- folliculostellate cells- support the cells and they secrete proteins which control the release of hormones-paracrine activity

-the anterior pituitary is regulated by chemical control...

-neurohormones- released from the nerve terminals of the hypothalamus into the capillary plexus of the internal carotid artery which enters the anterior pituitary through the hypothalamo-hypophyseal portal veins (travels down the pituitary stalk). The neurohormones diffuse from the veins and act on the local endocrine cells -Overall hypothalamic control is stimulatory for all anterior pituitary hormones except prolactin where it is inhibitory. The pulsatile release of hypothalamic releasing factors stimulate pulses of anterior pituitary hormones into the jugular vein.

The evidence that showed the hypothalamic control of the pituary was shown rabbits where injected with Indian ink and the result showed there was abundance in the pituary stalk showing there was a vascular connection between the hypothalamus and the pituitary gland. If the pituitary stalk was surgically removed all the target endocrine glands that the anterior pituitary gland control undergo atrophy but they regrow to orginal size when the stalk is reconnected.

Cells have a rich capillary network- endothelial lining of capillaries are fenestrated

Systemic hormones: hormones released by the target tissues of the anterior pituitary lobe exert a mostly negative feedback control

Paracrine interactions: in the anterior pituitary

Hormones released by the anterior pituitary

1) Thryotroph cells (Hypothalmic-pituitary-thyroid axis)

-Thyroid stimulating hormone/ thyrotrophin secreted by thryotroph cells

Chemical nature TSH-glycoprotein hormone made up of alpha and beta subunits.

Receptors: G protein coupled to cAMP on thyroid gland follicular cells

Actions: TSH acts in the thyroid and stimulates thyroid hormone production. It also increases iodine uptake by thyroid which is required for thyroid hormone production and stimulates thyroid growth

Control: TSH release is stimulated by thryotrophin releasing hormone from the hypothalamus whose secretion is also stimulated by cold and by stress via the CNS. TSH is secreted in pulses with a diurnal rhythm.

-there is also a systemic control and TSH release is inhibited by T3 and T4 by negative feedback.

Dysfunction: TSH disorders are very rare

2) Corticotroph cells

-secrete Adreno cortico Trophic Hormone (ACTH) /corticotrophin

Chemical nature: polypeptide hormone cleaved from the prohormone ProOpioMelanoCortin

Receptors: G protein coupled to cyclic AMP in adrenal cortex- binds to MCR2 receptors on fasiculate and reticularis layers of adrenal cortex

Actions

-stimulates production and secretion of cortisol-glucocorticoid steroid hormone from the cortex of adrenal gland- responsible for regulation of glucose metabolism

-ACTH- increased cyclic AMP- protein kinase A- phosphorylation of cholesterol side chain cleavage enzyme- increased conversion of cholesterol into pregnenolone (this is the rate limiting step of cholesterol synthesis)

-Over long period of times- ACTH- increased synthesis of various enzymes- induction- P-450 enzymes- needed in the synthesis of cortisol, LDL receptors, HMG-CoA

-minor effect on aldosterone- binds to glomerulsoa cells of the adrenal cortex- triggers synthesis of deoxycorticosterone- precursor of aldosterone- aldosterone- mineralocorticoid- increase reabsorption of ions and water- increase blood pressure

-increase in the adrenal sex steroids

-stimulates growth of adrenal cortex-when one adrenal gland is removed the adrenal gland on the opposite side grows to double the size. This is because less cortisol is produced which results in an increase in ACTH. This stimulates the growth to compensate for the surgical loss.

-melanocyte stimulating hormone is also cleaved from the proopiomelanocortin and is released by corticotrophs. MSH stimulates skin pigmentation

Control

-release of ACTH is stimulated by corticotrophin releasing hormone (CRH) from the hypothalamus-stress/hypoglycaemia- binds to GPCR on corticotroph cell membranes- alpha subunit of Gs activating adenylate cylase- increased cylic AMP- protein kinase- VGCC- exocytososis of ACTH into systemic veins

-Pulsatile secretion of corticotrophin releasing hormone from hypothalamus- receives input from retina- very high concentration of ACTH early in the morning and diminishes throughout the day- so secretion of ACTH is diurnal

-CRH secretion is also stimulated by stress so increased ACTH with stress

-The CRH also stimulates division of the corticotroph cells

-Vasopressin hormone synthesised in the hypothalamus- induces release of adrenocorticotrophin hormone

-systemic control by cortisol- glucocorticoid negative feedback- if the concentration exceeds a threshold level- negative feedback on the anterior pituitary corticotroph cells- cortisol diffuses through the plasma membrane of corticotrophs and binds to cytosolic receptor- moves into the nucleus- binds to glucocorticoid response element in promoter region- decreased gene expression of CRH receptors, decreased expression of ACTH

-The cortisol inhibits the release of presynthesised of ACTH stored in the vesicles

-cortisol also has a negative feedback on the hypothalamus- decrease in the synthesis and secretion of CRH

Dysfunctions

Cushing’s disease: excess ACHTH from corticotrophinoma pituitary tumours (Unable to respond to homeostatic feedback loops) cause excess glucocorticoid secretion- wide range of glucocorticoid receptors wide range of side effects: diabetes mellitus, proximal muscle wasting, decreased immunity to infections, osteoporosis, truncal obesity- excess gluconeogensis, stimulation of fatty acid breakdown, amino acid mobilisation

-can be caused due to steroids—prenisolone

-treatment: removal of adrenal or pituitary adenomas

Addison’s disease: deficiency of the ACTH causes glucocorticoid deficiency- disease is often due to an infectious disease (tuberculosis in humans)/ autoimmune destruction of the adrenal cortex- cardiovascular disease/weakness/lethargy/diarrhea

Nelson’s syndrome: rapid enlargement of a pituitary adenoma, that occurs after the removal of 2 adrenal glands. Removal of both adrenal glands is used to treat cushing’s and eliminates production of cortisol- lack of cortisol’s negative feedback causes the pituitary oedema to grow rapidly- increased growth of the pituitary gland leads to compression of the brain and the production of excess ACTH and MSH- ingreased pigmentation via excess MSH

3) Gonadotrophs

-secrete LH (Luteinizing hormone), FSH (follicle stimulating hormone)

Chemical nature: glycoprotein hormone made up of an alpha and beta subunit. The alpha subunit is common with that in TSH.

Receptors: G protein coupled to cyclic AMP in the ovary and testes

Actions

Female

-FSH acts on Granulosa cels

- stimulate their division,

- secretion of antral fluid

-activate them to convert the androgens secreted by thecal cells to oestrogen by stimulating production of aromatase,

- stimulation of production of peptide hormones, growth factors

-stimulate production of LH receptors

-LH acts on LH receptors on Theca interna cells- stimulates production of androgens (androstenedione) via cyclic AMP, also causing them to grow, divide

-LH also acts on mural granulosa cells in dominant follicle which have been selected for ovulation during a cycle

Male

-LH controls testerone production by Leydig cells- induces secondary characteristics, maturation of seminiferous tubules, growth of testes, stimulation of start of spermatogenesis

-FSH stimulates Sertoli cells –growth, secrete inhibin, ABH-stimulates and initiates spermatogenesis

Control:

- Hypothalmic: LH and FSH release...