BC3070 Biochemical Endocrinology



BS2050 Human Physiology

Basic Principles of Endocrinology

An Endocrine Gland is a collection of specific cells (endocrine cells) organised into a tissue whose major function is to produce hormones in response to a particular physiological signal or signals. The hormones may be stored in the endocrine gland in secretory granules as is the case with catecholamine, peptide and polypeptide hormones or synthesised on demand as is the case for steroid and thyroid hormones.

A Hormone is a specific chemical substance produced in specialized endocrine cells and is released into the bloodstream where it can exert its effects on different cell types in other tissues. These are referred to as Target Cells and are characterized by the presence of a specific hormone receptor which is involved in the transduction of the hormonal signal. Hormonal effects may be general i.e. many different types of cell may be affected, often in different ways (e.g. insulin), or they may be quite specific effect on a single target cell (e.g. the effects of LH on the Leydig cells in the testis).

Hormones have a diversity of chemical structure and size ranging from the glycoprotein hormones (LH, FSH, hCG, TSH), larger polypeptides (insulin, ACTH, Gastrin, CRH), smaller modified peptides (TRH, GnRH), the lipophilic steroid hormones (testosterone, oestradiol, cortisol , aldosterone), hormones derived from amino acids (adrenaline and thyroxine) and those derived from fatty acids like prostaglandins.

Hormones are produced and secreted in small quantities (ng – mg range per day) and the blood plasma concentration is low (1 pM – 10nM depending on the hormone) but changes may be 10 –100 fold in response to a physiological signal. The physiological or metabolic response to a hormonal signal is greatly amplified compared to the change in hormone concentration.

Hormones are subject to rapid turnover, so that hormone levels rapidly rise in response to a physiological signal and as soon as the need for the signal disappears, the hormone is rapidly removed from the system. The physiological effects of the hormone may not appear until well after the hormone levels have returned to their original level.

The concentration of hormone in the blood is normally determined by its rate of secretion by the endocrine gland. The rate of degradation or modification of a hormone, and thus its inactivation, is usually a fairly constant process and can occur in different sites within the body (e.g. liver and kidney).

The effect of a hormone on a target cell is dependent on two factors:

• The capacity of the tissue to respond to the hormone which, in turn, is dependent on the presence of a high affinity receptor, which binds hormone at low concentrations of the ligand (hormone). These receptors may be associated with the outside of the plasma membrane (e.g. peptide, polypeptide and catecholamine receptors) or in the cell cytoplasm or nuclei, e.g. steroid and thyroid hormones). The basic principles of kinetic analysis (e.g. Scatchard Analysis) of ligand-binding receptor proteins can also be applied to hormone-receptor interactions.

• The concentration of hormone in the blood which, as mentioned can change about 10 –100 fold. This change is normally induced by a small range of concentrations on either side of the dissociation constant (Kd) for the hormone-receptor interaction.

There is normally a sigmoidal relationship between the hormonal concentration and its effect. At low concentrations the hormone level can change without much effect, until it reaches a threshold concentration where the magnitude of the physiological effect is directly proportional to the hormone concentration. At higher concentrations this proportionality disappears and the physiological effect reaches a maximum. An useful measurement is the concentration of hormone at which half of the maximal physiological effect is found. (This is often estimated by plotting the magnitude of the physiological response against the Log10[Hormone]). This is usually closely related to the Kd of the hormone-receptor interaction.

Note: The same hormone can have different qualitative and quantitative effects on different types of cell. Also the same hormone can have different effects on one type of cell at different concentrations.

Hormones regulate one or more existing cellular functions:

• Metabolism via alterations in enzyme activities (positive or negative effects)

• Membrane permeability to specific ions and metabolites

• Gene transcription of specific gene products, in turn regulating cell-specific protein synthesis

• induce secretory activity of cell

• mitotic cell division

There is a shift in the timeframe between the change in hormone concentration which may be all over within seconds and the ensuing physiological effects which may take several minutes, hours or sometimes days to manifest themselves.

The functions of hormones are many and varied but some general examples are given below:

• The maintenance of homeostasis i.e. the maintenance of the composition of the tissues and body fluids for the benefit of the organism as a whole (e.g. insulin and glucagon regulate blood glucose within strict limits by integrated effects on glucose metabolism various tissues).

• Hormones allow an appropriate response to external stimuli (e.g. the effect of adrenaline in the fight or fright response).

• Some hormones control cyclic and developmental changes (e.g. they regulate the growth of the individual, circadian rhythms or sexual function such as the menstrual cycle, pregnancy, spermatogenesis etc)

• Hormones can cause changes in brain function and behaviour

• Hormones often have synergistic effects – on their own they are inactive or poorly active but, at the same concentration, in combination with one or more other hormones, they produce a full physiological effects.

The most common regulatory mechanism for controlling hormone secretion and thus the hormone concentration is the Negative Feedback Loop. This is where a hormone or metabolite, produced as part of the physiological response by the target tissue, is released into the bloodstream, is transported to the endocrine cell where it limits the further secretion of hormone.

D R Davies Jan 2005

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