1. Endocrine glands & its Regulation
Dr. Rahul B. Patil
Assistant Professor in Zoology
Veer Wajekar ASC College, Phunde

2. General Organization of Mammalian Endocrine System

3. Hormone: Classification
Category # 1. According to Chemical Nature:
(a) Steroid Hormones:
These are made up of lipids, which basically derived from cholesterol, e.g. Testosterone, Estrogen, Proges­terone etc.
(b) Amine Hormones:
These hormones are made up of amines. Amine hor­mone is derivative of the amino acid tyrosine.
e.g. T3, T4, epinephrine, norepinephrine.
(c) Peptide Hormones:
These hormones are made up of few amino acid resi­dues only and present as simple lin­ear chain.
e.g. Oxytocin and vasopressin both consist of only 9-amino acid residues only.
(d) Protein Hormones:
These hormones are also made amino acid residues which are much more in numbers. They represent primary, secondary and tertiary configuration.
e.g. Insulin, glucagon, STH etc.
(e) Glycoprotein Hormones:
These hor­mones are glycoprotein in nature. They are conjugated protein where carbohydrate groups are mannose, galactose, fucose etc.
e.g. LH, FSH, TSH etc.

4. Hormone: Classification
Category # 2. On the Basis of Mechanism of Action:
(a) Group I hormones:
These hormones bind to intracellular receptors to form hormone-receptor complexes (HRC), through which their biochemical functions are mediated. These hor­mones are lipophilic in nature and are derivatives of cholesterol (except T3 and T4). They are found in circula­tion in association with transport pro­teins and possess relatively longer half-lives (hours or day). e.g. Estrogen, Progesterone, Test­osterone, T3, T4 etc.
(b) Group II hormones:
These hormones bind to cell surface (plasma mem­brane) receptors and stimulate the release of certain molecules, namely the second messengers which in turn, perform the biochemical functions. Thus, hormones themselves are lipophobic in nature, usually trans­ported in the free form and possess short half-lives (in minutes).
Group II hormones are subdivided into three categories on the basis of chemical nature of second messen­gers:
(i) The second messenger is cAMP. e.g. ACTH, FSH, LH etc.
(ii) The second messenger is phospholipid/inositol/Ca++.
e.g. TRH, GnRH, Gastrin etc.
(iii) The second messenger is un­known.
e.g. STH, LTH, Insulin, Oxytocin etc.

5. Hormone: Classification
Category # 3. According to Nature of Action:
(a) Local Hormones:
These hormones have got specific local effects by paracrine secretion.
e.g. Testosterone.
(b) General Hormones:
These hormones are transported by circulation to the distal target organ/tissue.
e.g. Insulin, Thyroid hormone etc.

6. Hormone: Classification
Category # 4. According to Effect:
(a) Kinetic Hormones:
These hormones may cause pigment migration, muscle contraction, glandular secre­tion etc.
e.g. Pinealin, MSH, Epinephrine etc.
(b) Metabolic Hormones:
These hor­mones mainly changes the rate of metabolism and balance the reac­tion.
e.g. Insulin, Glucagon, PTH etc.
(c) Morphogenetic Hormones:
These hormones are involved in growth and differentiation.
e.g. STH, LTH, FSH, Thyroid hor­mones etc.

7. Hormone: Classification
Category # 5. On the Basis of Stimulation of Endocrine Glands:
(a) Tropic Hormones:
These hormones stimulate other endocrine glands for secretion.
e.g. TSH of pituitary stimulates se­cretion of thyroid gland.
(b) Non-tropic Hormones:
These hor­mones exert their effect on non-endocrine target tissues.
e.g. Thyroid hormone increases the O2 consumption rate and metabolic activity of almost every cells.

8. Properties of Hormones
Hormones are secreted by endocrine cells. 
Hormones are chemical messengers.
The are chemical signals that circulate in the body fluids. 
The hormones regulate the behavior of the target cells. 
Hormones, unlike enzymes do not catalyze any reaction. 
They are secreted only when needed, they are not stored prior to requirement. 
Hormones may be proteinaceous or non-proteinaceous in nature (amino-acids or steroids). 
The secretion of hormones is regulated by the nervous system through the feed back effect. 
Hormones usually cause long term effects like change in behavior, growth, etc.
The hormones function is to stimulate or inhibit the target organs.

9. Mechanism of Hormone Action
The following points highlight the two important mechanisms of hormone action. The mechanisms are:
1. Mode of Protein Hormone Action through Extracellular Receptors
2. Mode of Steroid Hormone Action through Intracellular Receptors.

10. (i) Formation of Hormone Receptor Complex:
Mechanism 1: Mode of Protein Hormone Action through Extracellular Receptors:
(i) Formation of Hormone Receptor Complex:
Every hormone has its own receptor.
The number of receptors for each hormone varies.
Insulin receptors for most cells is less than 100 but for some liver cells their number may be more than 1,00,000.
The molecules of amino acid derivatives, peptides or polypeptide protein hormones bind to specific receptor molecules located on the plasma membrane to form the hormone receptor complex.

11. Formation of Hormone Receptor Complex

12. (ii) Formation of Secondary Messengers—the Mediators:
The hormone-receptor complex does not directly stimulates adenyl cyclase present in the cell membrane. It is done through a transducer G protein. Alfred Gilmans has shown that the G protein is a peripheral membrane protein consisting of ∝, β and γ subunits (Fig 22.19).
It interconverts between a GDP form and GTP form. In muscle or liver cells, the hormones such as adrenaline bind receptor to form the hormone-receptor complex in the plasma membrane.
The hormone- receptor complex induces the release of GDP from the G protein. The α- subunit bearing GTP separates from the combined β and у subunits. The β and у subunits do not separate from each other. The activated β and γ subunits of G protein activate adenyl cyclase. The activated adenyl cyclase catalyses the formation of cyclic adenosine monophosphate (cAMP) from ATP.

14. The hormone is called the first messenger and cAMP is termed the second messenger.
The hormones which interact with membrane-bound receptors normally do not enter the taget cell, but generate second messengers (e.g., cAMP).
Besides, cAMP, certain other intracellular second messengers are cyclic guanosine monophosphate (cGMP), diacyl-glycerol (DAG), inositol triphosphate (IP3) and Ca++ responsible for amplification of signal.
Earl W. Sutherland Jr ( ) discovered cAMP in He got Nobel prize in physiology of medicine in 1971 for his discovery, “Role of cAMP in hormone action”.

15. (iii) Amplification of Signal:
Single activated molecule of adenyl cyclase can generate about 100 cAMP molecules. Four molecules of cAMP now bind to inactive protein-kinase complex to activate protein-kinase A enzyme.
Further steps as shown in involve cascade effect. In cascade effect, every activated molecule in turn activates many molecules of inactive enzyme of next category in the target cell. This process is repeated a number of times.
In the cytoplasm a molecule of protein kinase A activates several molecules of phosphorylase kinase. This enzyme changes inactive form of glycogen phosphorylase into active one.
Glycogen phosphorylase converts glycogen into glucose-1 phosphate. The latter changes to glucose. As a result single molecule of ademaline hormone may lead to the release of 100 million glucose molecules within 1 to 2 minutes. This increases the blood glucose level.

16. (iv) Antagonistic Effect:
The effect of hormones which act against each other are called antagonistic effects. Many body cells use more than one second messenger. In heart cells cAMP acts as a second messenger that increases muscle cell contraction in response to adrenaline, while cGMP acts as another second messenger which decreases muscle contrac­tion in response to acetylcholine.
Thus the sympathetic and parasympathetic nervous systems achieve antagonize effect on heart beat. Another example of antagonistic effect is of insulin and glucagon. Insulin lowers blood sugar level and glucagon raises blood sugar level.

17. (v) Synergistic Effect:
When two or more hormones complement each other’s actions and they are needed for full expression of the hormone effects are called synergistic effects.
For example, the production and ejection of milk by mammary glands require the synergistic effects of oestrogens, progesterone, prolactin and oxytocin hormones.

18. Mechanism # 2: Mode of Steroid Hormone Action through Intracellular Receptors
Steroid hormones are lipid-soluble and easily pass through the cell membrane of a target cell into the cytoplasm. In the cytoplasm they bind to specific intracellular receptors (proteins) to form a hormone receptor complex that enters the nucleus.
In the nucleus, hormones which interact with intracellular receptors (e.g., steroid hormones, iodothyromines, etc.) mostly regulate gene expression or chromosome function by the interaction of hormone-receptor complex with the genome.
Biochemical actions result in physiological and developmental effects (tissue growth and differentiation, etc.). In-fact the hormone receptor complex binds to a specific regulatory site on the chromosome and activates certain genes (DNA).
The activated gene transcribes mRNA which directs the synthesis of proteins and usually enzymes in the cytoplasm. The enzymes promote the metabolic reactions in the cell. The actions of lipid soluble hormones are slower and last longer than the action of water- soluble hormones.

19. Mechanism # 2: Mode of Steroid Hormone Action through Intracellular Receptors

20. Role of Hormones as Messengers and Regulators (Role of Hormones in Homeo­stasis):

21. Hormones as Messengers [Hypothalamus-hypophysial (pituitary) Axis]:
Hypothalamus is a part of the fore brain. Its hypothalamic nuclei— masses of grey matter containing neurons, are located in the white matter in the floor of the third ventricle of the brain. The neurons (neurosecretory cells) of hypothalamic nuclei secrete some hormones called neurohormones (releasing factors) into the blood.
The neurohormones are carried to the ante­rior lobe of the pituitary gland (hypophysis) by a pair of hypophysial portal veins. In the pituitary gland (hypophysis) the neurohormones stimulate it to release various hormones. Hence the neurohormones are also called “releasing factors”.

22. Hormones as Regulators (Feed Back Control):
Homeostasis means keeping the internal environment of the body constant.
Hormones help in maintaining internal environment of the body.
When the secretion of hormones is under the control of factors or other hormones it is called feedback control.
The regulation of secretion of thyroxine from the thyroid gland is an example of such feedback control mechanism.

23. Types of Feed back control
(i) Positive Feed Back Control:
If the level of thyroxine is less than normal limits in the blood, thyroxine level stimulates the hypothalamus to secrete more of TRH which results in increased secretion of TSH which in turn stimulates increased secretion of thyroxine. Such regulatory effect is called positive feedback control.
(ii) Negative Feed Back Control:
The thyrotropin releasing hormone (TRH) from the hypothalamus stimulates the anterior lobe of the pituitary gland to secrete the thyroid stimulating hormone (TSH).
The TSH in turn stimulates the thyroid gland to secrete thyroxine. A high amount of thyroxine in the blood exerts an inhibitory effect on hypothala­mus in such a way that less of TRH and TSH is produced respectively. This eventually results a decrease in thyroxine. This is called negative feedback control.