of the gut, amphibian urinary bladder and skin, and the gills of fish. The
neurohypophysial peptides and corticosteroids may initiate such effects.
The precise manner (in terms of cells and molecules) in which any hormone
may exert such actions is unknown, but over the last decade enough information
has become available to indicate that the process is very complex. The information
that is available in several instances has provided a framework of knowledge about
these final events in the actions of hormones and has given us plenty of ideas about
what to look for at the effector sites. This is particularly applicable to the mechanisms of action of the neurohypophysial and corticosteroid hormones on osmoregulatory processes. The action of a hormone at its effector site involves a series
of chemical and metabolic events that culminate in one of the types of responses
just listed. The preceding events can be broadly classified as:
1. The approach of the hormone to the vicinity of the effector tissue. This may
be influenced by such factors as its concentration, size, shape (steric configuration),
electrical charge and polar or non-polar nature.
2. The molecular interaction of the hormone with its 'receptor'. The 'receptor'
is a pharmacological concept, which is envisaged as a chemical substance, or group,
that complements chemically, sterically and electrically, the structure of the hormone, so that the two can interact in a specific way. Other substances can also
sometimes interact with such receptors, but may initiate little or no effect, though
they may exclude the hormone from this site and so prevent its action. The receptor
may be an enzyme, or part of an enzyme-system, or occupy some strategic structural site in the cell. Little is known about their chemical nature, though in some
instances, such as the receptors for neurohypophysial hormones, oestrogens and
insulin, it is suspected that a sulphydryl group may be involved. The isolation of
specific receptors in vitro, is the ultimate aspiration of many pharmacologists and
endocrinologists. Receptors are thought to be in the cell membrane, and in specific
sites within the cell such as in the nucleus. In the instance of the oestrogens and
corticosteroids, the evidence for a nuclear site is strong. Receptor sites at the cell
surface have been favoured for other hormones, but the evidence is usually weak
and largely intuitive; they may well be located there nevertheless.
3. Secondary reactions follow as a direct result of the hormone-receptor interaction. Such reactions presumably serve the purpose of forming metabolites to be
used for 'triggering' the molecular machinery of the ultimate effector, as well as
amplifying the small energetic changes associated with the initial event. Our
knowledge of such secondary reactions is very incomplete, though it does warn
us of considerable complexity. An intermediate associated with such processes is
the nucleotide cyclic adenosine-3',5'-monophosphate (cyclic AMP). This is formed
in effector tissues as a result of the actions of a number of hormones like corticotrophin, vasopressin, adrenaline and glucagon. Cyclic AMP arises from ATP by the
action of adenyl cyclase, an enzyme that is activated in some way by the hormone.
Another intermediate is ribonucleic acid (messenger-RNA), which is synthesizeci
at increased rates in the presence of oestrogens and corticosteroids, and mediates
cytoplasmic genetic translation for the synthesis of specific proteins.
4. The effector response is finally 'triggered', but how this is done by the mediation of cyclic AMP or the actions of newly synthesized proteins is not always
clear. Cyclic AMP can activate phosphorylase, which in metabolic responses like
81
neurohypophysial peptides and corticosteroids may initiate such effects.
The precise manner (in terms of cells and molecules) in which any hormone
may exert such actions is unknown, but over the last decade enough information
has become available to indicate that the process is very complex. The information
that is available in several instances has provided a framework of knowledge about
these final events in the actions of hormones and has given us plenty of ideas about
what to look for at the effector sites. This is particularly applicable to the mechanisms of action of the neurohypophysial and corticosteroid hormones on osmoregulatory processes. The action of a hormone at its effector site involves a series
of chemical and metabolic events that culminate in one of the types of responses
just listed. The preceding events can be broadly classified as:
1. The approach of the hormone to the vicinity of the effector tissue. This may
be influenced by such factors as its concentration, size, shape (steric configuration),
electrical charge and polar or non-polar nature.
2. The molecular interaction of the hormone with its 'receptor'. The 'receptor'
is a pharmacological concept, which is envisaged as a chemical substance, or group,
that complements chemically, sterically and electrically, the structure of the hormone, so that the two can interact in a specific way. Other substances can also
sometimes interact with such receptors, but may initiate little or no effect, though
they may exclude the hormone from this site and so prevent its action. The receptor
may be an enzyme, or part of an enzyme-system, or occupy some strategic structural site in the cell. Little is known about their chemical nature, though in some
instances, such as the receptors for neurohypophysial hormones, oestrogens and
insulin, it is suspected that a sulphydryl group may be involved. The isolation of
specific receptors in vitro, is the ultimate aspiration of many pharmacologists and
endocrinologists. Receptors are thought to be in the cell membrane, and in specific
sites within the cell such as in the nucleus. In the instance of the oestrogens and
corticosteroids, the evidence for a nuclear site is strong. Receptor sites at the cell
surface have been favoured for other hormones, but the evidence is usually weak
and largely intuitive; they may well be located there nevertheless.
3. Secondary reactions follow as a direct result of the hormone-receptor interaction. Such reactions presumably serve the purpose of forming metabolites to be
used for 'triggering' the molecular machinery of the ultimate effector, as well as
amplifying the small energetic changes associated with the initial event. Our
knowledge of such secondary reactions is very incomplete, though it does warn
us of considerable complexity. An intermediate associated with such processes is
the nucleotide cyclic adenosine-3',5'-monophosphate (cyclic AMP). This is formed
in effector tissues as a result of the actions of a number of hormones like corticotrophin, vasopressin, adrenaline and glucagon. Cyclic AMP arises from ATP by the
action of adenyl cyclase, an enzyme that is activated in some way by the hormone.
Another intermediate is ribonucleic acid (messenger-RNA), which is synthesizeci
at increased rates in the presence of oestrogens and corticosteroids, and mediates
cytoplasmic genetic translation for the synthesis of specific proteins.
4. The effector response is finally 'triggered', but how this is done by the mediation of cyclic AMP or the actions of newly synthesized proteins is not always
clear. Cyclic AMP can activate phosphorylase, which in metabolic responses like
81