Anterior pituitary and their hormones and drugs

Introduction:

Anterior pituitary is an endocrine gland which secretes number of important regulatory hormones. These hormones (peptide in nature) act as extracellular receptors located on the target cells.

Regulation of anterior pituitary hormones regulated by hypothalamus through release stimulatory and release inhibitory hormones which transported via hypothalamo-hypophyseal portal system.

Each hormone secreted via anterior pituitary according to their staining characteristics of either acidophilic or basophilic.

Anterior  pituitary secretes hormones are:

1. Acidophilic cells-

Somatotropes > Growth hormone

Lactotropes > Prolactin

2. Basophilic cells-

Thyrotropes > Thyroid stimulating hormone

Corticosteroids > Adrenocorticotropic hormone (ACTH)

Gonadotropes > Follicle stimulating hormone (FSH) and Luteinizing hormone (LH)

Growth hormone:

It is 191 amino acid, single chain peptide of molecular weight 22000.

Physiological function:

During childhood and adolescene, growth hormone required for normal growth and attainment of adult stature. Growth hormone promotes growth of bones and all organs ( except brain, eyes and sexual organs).

Growth hormone promotes retention of nitrogen, calcium and other tissue constitutes to enhance production of protoplasm and nitrogen retention helpful in the synthesis of protein that utilized by the body.

Growth hormone also promotes carbohydrates and fat metabolism throughout the life.

Mechanism of action:

Growth hormone act on cell surface JAK-STAT binding protein kinase receptors which present on all types of cells.

Binding of growth hormone to the receptor results in the conformational changes and activation of intracellular domain to associates with cytoplasmic JAK-STAT tyrosine protein kinase resulting in metabolic as well as regulation of gene expression.

Growth hormone induced indirect effect through releasing of somatomedins or IGF-1 (Insulin like growth factor) from liver which are extracellular mediator of growth hormone response.

IGF-1 promotes:

> Lipogenesis

> Glucose uptake by muscle

Growth hormone promotes:

> Lipolysis in adipose tissue

> Gluconeogenesis, glycogenolysis in liver and decreased glucose uptake by muscle.

Regulation of secretion:

Regulation of secretion of hormones are regulated from anterior pituitary by hypothalamus that releasing stimulatory (GHRH) and inhibitory (GHIH) hormones.

These hormones from hypothalamus act via GPCR (G- protein coupled receptor).

GHRH > Growth Hormone Releasing Hormone

GHIH > Growth Hormone Inhibiting Hormone

Pathological involvement:

Excess production of growth hormone (GH), results Gigantism in children and acromegaly in adults.

Less production of growth hormone (GH), results pituitary dwarfism and in adults low muscle and bone mass, decrease work capacity, lethargy and increased cardiovascular risk.

Uses:

1. Pituitary dwarfism:

Pituitary dwarfism is due to deficiency of growth hormone (GH) which noticed earlier in children as subnormal growth. In this condition, prefer recombinant human growth hormone (rhGH) therapy.

2. Turner syndrome:

Turner syndrome is the short stature of girls which is treated with rhGH combining with estrogen and androgen therapy.

3. GH deficiency in adults:

Growth hormone deficiency cause low bone and muscle mass, results in lethargy, decrease work capacity. In this condition also prefer rhGH.

4. AIDs related wasting:

Due to AIDs treatment, low muscle and bone mass and lean body posture. Treated by use of rhGH therapy.

5. Mecasermin:

In this situation children not response to rhGH, give recombinant human IGF-1. 

Prolactin:

It is 199 amino acid, single chain peptide of molecular weight is 23000.

Physiological functions:

Prolactin conjugate with estrogen and progesterone and several other hormones to cause growth and development of breast during pregnancy. It promotes proliferation of ductal as well as acinar cells in the breast and induces the synthesis of milk protein and lactose.

After parturition, prolactin induces milk production.

Prolactin promotes suppression of hypothalamus - pituitary gonadal function of Inhibiting GnRH.

Continuous high level of prolactin during breastfeeding responsible for lactation and Inhibition of ovulation and infertility for several months of postpartum.

Mechanism of action:

Prolactin act on cell surface JAK-STAT binding protein kinase receptors which present on all types of cells.

Binding of prolactin to the receptor results in the conformational changes and activation of intracellular domain to associates with cytoplasmic JAK-STAT tyrosine protein kinase resulting in metabolic as well as regulation of gene expression.

Regulation of secretion:

Prolactin secretion of Inhibition control by hypothalamus through PRIH which is a dopamine that act on pituitary lactotrope D2 receptors. Prolactin level low in childhood girl, increase level in girl at puberty and higher in adult female and peak level at pregnancy.

PRIH > Prolactin Inhibiting Hormone

Note: Higher prolactin secretion is maintained by suckling, if breastfeeding is discontinued then level falls.

Pathological involvement:

Hyperprolactinaemia is responsible for galactorrhoea - amenorrhoea - infertility syndrome in women.

In male, it cause loss of libido and depression of fertility.

Uses:

1. Hyperprolactinaemia

2. Acromegaly

3. Parkinsonism

Gonadotropins:

Anterior pituitary secretes two gonadotropins that are FSH and LH.

Both are glycoprotein containing 23 - 28% sugar and two peptide chains, alpha chain of both hormones are same but beta chain of FSH has 111 amino acid and LH has 121 amino acid.

FSH > Follicle Stimulating Hormone

LH > Luteinising Hormone

Physiological functions:

FSH > In female, it induces follicular growth, development of ovum and secretion of estrogen.

In male, it cause spermatogenesis and has a tropic influence on seminiferous tubules.

Ovarian and testicular atrophy occur in the absence of FSH.

LH > In female, induces preovulatory ripening of graafian follicles and trigger ovulation of ripen or ruptured follicles and sustain the corpus luteum till next menstrual cycle. Progesterone secretion enhanced by the influence of LH.

In male, Testosterone secretion enhanced by the action of LH from interstitial cells.

Mechanism of action:

LH and FSH act via G- protein coupled receptors (GPCRs), increase production of cAMP that cause release of FSH and LH.

Pathophysiology involvement:

Disturbances in gonadotropins secretion,

Excess secretion cause polycystic ovary syndrome in women.

Less secretion cause amenorrhoea or irregular menstrual cycle.

Uses:

1. Amenorrhoea:

Amenorrhoea is the absence of periods or irregular menstrual cycle in women.

2. Infertility:

Infertility Is due to deficient production of Gns by pituitary.

3. Male hypogonadism:

It manifests as delayed puberty or defective 

spermatogenesis producing oligozoospermia and male sterility.

Thyroid stimulating hormone:

It is a 210 amino acid, two chain peptide of molecular weight 30000.

Physiological functions:

Thyroid stimulating hormone stimulates thyroid gland to synthesize and release thyroid hormones that are thyroxine (T4) and triiodothyronine (T3).

> Thyroid hormones promotes the hyperplasia and hypertrophy of thyroid follicles.

> Increase blood supply to thyroid glands.

> Promotes trapping of iodide and incorporation into T3 and T4 by peroxidase action.

Mechanism of action:

Thyroid stimulating hormone (TSH) act via receptors are G- protein coupled receptors on thyroid cells. Binding promotes activation of intracellular domain attached with adenylyl - cyclase to increase cAMP production results release of thyroid hormones from thyroid gland and show further action.

Regulation of secretion:

Regulation of secretion of thyroid hormones controlled by pituitary as well as hypothalamus. Thyroid hormone release give negative feedback to hypothalamus as well binds to TRH receptors on pituitary cause inhibits the secretion of thyroid hormones.

Pathophysiology involvement:

Higher or lower secretion of thyroid hormones due inappropriate TSH secretion. Higher secretion cause Grave disease and toxic nodular goiter.

Less secretion results hypothyroidism.

Uses:

Hypothyroidism due to TSH deficiency, treat with thyroid hormone therapy.

Adrenocorticotropic hormones:

It is 39 amino acid, single chain peptide fo molecular weight 4500.

Physiological functions:

Adrenocorticotropic hormone (ACTH) stimulates steroidogenesis in adrenal cortex for the production of glucocorticoid, mineralocorticoid and weak androgen steroids.

Mechanism of action:

ACTH promotes steroidogenesis in adrena cortex via attached with receptors present on cortical cells, GPCR type receptor results increase cAMP cause release of ACTH.

Regulation of secretion: