Objectives of 1st lecture The student should be able to: define hormones & classify them according to their (1) chemical composition & (2) mechanism of action Take an idea about the major endocrine glands Know how hormone secretion is controlled
Hormone – is defined as a regulatory chemical substance secreted into the blood by an endocrine gland and acts in a far away site.Paracrine - regulatory molecules work without being transmitted by the blood – not endocrineHormone in blood can be present in three forms total ,bound to proteins & free
Chemical Classification of Hormones Protein hormones – Binds to the receptors on the surface of cell membrane; its effects are the most rapid of all the hormones2) Amine acid hormones –Same relatively fast receptor response as protein hormones. Examples are catecholamines and thyroid hormones. 3) Steroid hormones – Binds to the intracellular receptors; slow actions, examples are Gonadal hormones and adrenal cortex hormones
Mechanism of Hormone Action All hormone action is receptor mediated Hormone binding to specific receptor results in conformational change in receptor that conveys a signal to target cell Another classification of hormones is according to their receptor location into two groups: Group I: Intracellular Receptors Group II: Cell surface receptors
Group I: Intracellular Receptors: Diffuse through the membrane of cells forming HR-complex inside the cells which undergo structural changes that enhance the binding of complex to DNA of the cell results in gene transcription (mRNA production) which affects metabolic response. Ex; Steroid and thyroid hormones
Group II: Cell surface receptors: These are protein-derived hormones that are water-soluble compounds so they cannot diffuse inside the cell but they bind to surface receptors and the signals transmitted intracellularly through the second messenger, (hormone is the first messenger). Example; Peptide hormones
Classified according to their second messengers into 4 subgroups: Subgroup (A): act by increasing cAMP level inside the cells through activation of cell membrane enzyme (adenylate cyclase). Subgroup (B) act by increasing cGMP level inside the cells through activation of guanylate cyclase Subgroup (C) the second messenger is phosphoinositol e.g. ADH Subgroup (D) the second messenger is unknown for hormones
Endocrine system control (axes and feedback loops): Hypothalamic-Pituitary Axes: Three main axes involving hypothalamus and pituitary control much of endocrine system They operate by negative feedback (Short and long loops) Hypothalamic-Pituitary-Thyroid axis (HPT) Hypothalamic-Pituitary-Adrenal axis (HPA) Hypothalamic-Pituitary-Gonadal axis (HPG)
The mechanism starts with neural signals which stimulate the production of releasing hormones (RH) from the hypothalamus. Each of these RH triggers anterior pituitary gland to produce its corresponding tropic hormone. These tropic hormones circulate in blood and act on their target gland or tissue to produce their products. prolactin is the exception because its secretion is normally inhibited (RHIH is high). Q: Are all hormones under Axis Control? Give examples?
Q) How many endocrine glands are there in the body, what classes do they fall in?
Control Mechanisms:- Are mechanisms that maintain normal level of hormones both in serum and tissues, these are: Negative feedback inhibition Neural stimulation i.e. stress Inherited rhythm (circadian rhythm); i.e. day & night levels
Endocrine Disease It is of two types: Primary endocrine disease: e.g. ovarian failure leading to very low oestrogen, w stimulate the hypothalamic (GnRH) or pituitary (LH and FSH) secretion. Secondary endocrine disease: e.g. Damage to hypothalamus causes deficiency of GnRH w causes no stimulation for pituitary hormone production, i.e. low levels of LH and FSH which leads to no hormonal action on target tissues (ovaries)----- low levels of serum estrogen and progesterone (in female).
The hypothalamus produces two types of hormones that are associated with posterior and anterior pituitary. Type 1: includes small molecules called regulatory H that are produced in the hypothalamus and are transported through blood network to anterior pituitary. Type 2 includes 3 peptide hormones that travel down to the posterior pituitary through nerve fibers where they are stored there. These hormones are: Arginine -vasopressin or Antidiuretic H (ADH) Oxytocin Neurophysin
Hypopituitarism: defined as failure of the gland to make one or more of ant. Pituitary hormones: GH, LH, FSH, TSH, ACTH, or prolactin (PRL) Defect in secretion of pituitary hormones is of two types: Isolated deficiency: only one or two hormones are deficient. (usual are gonadotropins and GH). Panhypopituitarism: in which all hormones of anterior pituitary are deficient due to pituitary tumors or infarction. In infarction, it may occur due to post-partum hemorrhage ((Sheehan's syndrome)). She develops lactation failure and difficulty in labour
What causes pituitary insufficiency (hypopituitarism)? Results from pituitary, hypothalamic, or parasellar disease w disrupt the normal function of H-P Unit by displacement, infiltration and destruction. Or due to surgical or radiotherapy treatment Q: If the pit stalk damaged, all ant pit hormones decrease except PRL. Why? Due to loss of inhibitory effect of hypothalamic Dopamine on lactotrophes. Q: What is the difference between functional and non functional pit tumors? Formal associated with excess hormonal secretion, latter associated with defect in hormonal secretions Q: What is the Houssay phenominon? It signify the relation between ant pit hormones and insulin. As hypopituitarism diminish the requirement of insulin in DM patients. Due to def of insulin antagonist hormones (GH, Corisol and thyroid hormones)
Hypopituitarism
The features are usually due to target gland failure e.g. deficiency of LH or FSH causes secondary hypogonadism, so leading to:Low Estrogen in females which results in amenorrhea, infertility, atrophy of secondary sex characters, and Low testosterone In males results in impotence and loss of libido, atrophy of secondary sex characters. Deficiency of GH and TSH causes growth retardation (dwarfism). Deficiency of ACTH causes secondary adrenocortical hypo-function.This type should be differentiated from the primary cause that's called Addison's disease, in which the adrenal gland itself is destroyed by bacterial infection or by auto-immune disease which means loss of adrenocortex function (cortisol↓).
In Addison's disease, there are low levels of cortisol with a very high level of ACTH. In contrast, in the secondary type, both cortisol and ACTH are on low levels. The second difference is that in primary, there is hyperpigmentation while in secondary there is no pigmentation (why?); because the low level of cortisol in Addison's there is loss of negative feedback inhibition, which results in excessive secretion of CRH and in turn ACTH. But ACTH is also stimulator of melanocytes which are important for melanin that give us dark pigmentation of skin and mucous membranes.Q: Why aldosterone H not affected by hypopiuitarism?Because aldosterone not controlled by H-P axis but by renin – angiotensin system
Features of hypopituitarism differ from children than adults? Children: growth failure Adolescents : Failure of sexual maturation Adults :signs of hypogonadism Elderly : Feature of hypothyroidism and adrenal insufficiency Frequency spectrum of hormonal deficiency as follow: GH> Gn> TSH> ACTH------ PRL rarely recognized The most critical hormone to be identify is ACTH and so cortisol because it is imp for life If diabetes insipidus features present this usually due to hypothalamic or pineal body origin If there is ant pit H def , WHY it is imp to exclude def of other Hs? Because replacement of thyroid H alone in patient with adrenal insufficiency may ppt adrenal crisis, also ADH def may be masked by adrenal insufficiency and after glucocorticoid replacement central DI appear and required specific treatment