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Hormone Receptors.

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Hormone Receptors
By Klaus Lubke, Ekkehard Schillinger, and Michael Topert[*]
Hormone receptors are proteins located on the cell membrane or in the cell cytoplasm.
Their function is to recognize and bind the respective hormone; the biological action of
the hormone originates from the hormone-receptor complex. Specific receptors have been
found for all known hormones. Monitoring the equilibration between hormone, receptor, and
hormone-receptor complex ("determination of receptor binding") permits quantitative determinations of hormones, allows the characterization of endocrinal disturbances, and contributes
to the elucidation of structure-affinity relationships.
1. Introduction
A common feature of all hormones is their participation
in the control of biological processes. Hormones function
by transmitting information which leads to a triggering of
cell-specific activities. They can only fulfil the role of a "first
messenger" if recognized by their target organs and distinguished from other compounds. A decisive step in the
recognition process is the binding of the hormone to its receptor (a protein). The biological activity of a hormone (or a
hormone analog) is determined by the concentration of the
hormone-receptor complex at the site of action and by the
intrinsic activity"S2' of the complex. The concentration of
the hormone-receptor complex depends upon the availability
of the hormone at the site of action and upon its affinity
for the receptor (Fig. I ) .
The former group includes all peptide and proteohormones,
the biogenic amines, and the prostaglandins, while the latter
group comprises all steroid hormones, thyroxine, and triiodothyronine.
2. The Hormone-Receptor Complex
The existence of specific hormone receptors and their importance in hormone action were postulated long
experimental detection of the receptors, present only in very
low concentration, was long thwarted by the lack of suitable
experimental methods, and only became possible once hormones could be labeled with sufficiently high specific radioactivity. In the early 1960s Jetisel7 er ul. used tritium-labeled
estradiol to characterize the first cytoplasmic (intracellular)
hormone re~eptor'~!
A few years later C ~ a t r e c u s u s [Lefkow~~,
itz et
and Goodfvierzd et a/.[" were able to detect the
first membrane-bound receptors using ACTH, insulin, and
angiotensin, respectively, labeled with radioactive iodine. Specific receptors were subsequently reported for all hormones
and concepts formulated for hormone-receptor binding and
its significance for hormonal action.
2.1. Definition of the Hormone Receptor
A hormone receptor has to fulfil a number of requirements[*]:
Fig. I. Factors aflecting the concentration of the hormone-receptor complex,
and hence the biological activity, iir riro.
The hormone-receptor complex may be formed on or inside
the cell. In the former case the hormone finds its specific
receptor on the surface ot the cell membrane. There is no
need for it to penetrate into the cell; instead it triggers an
intracellular process by binding to the membrane-bound receptor. In the latter case the hormone does have to penetrate
into the cell before a hormone-receptor complex can be formed.
Dr. K . Lubke, Dr. E. Schillinger, and Dr. M. Toper1
Forschungslaboratorien der Schering AG, BerlinIBergkamen
Mullerstrasse 170-178. D-1000 Berlin 65 (Germany)
1 ) The specificity of the receptor must be very high and
comply with known structure-activity relations.
2) The number of binding sites must be limited.
3 ) The occurrence of receptors in various tissues should
correlate with the response of the respective tissue to the
4) Owing to the very low physiological concentrations of
hormones the receptor must have a high affinity for the hormone.
5) Hormone-receptor binding must be reversible in order
to terminate the physiological effect and permit fresh stimulation.
It is important to distinguish between receptor binding,
characterized by high affinity with low capacity, and non-specific binding to other hormone-binding proteins. The latter
typically exhibits a low affinity at very high capacity.
2.2. Membrane-Bound Hormone Receptors
The intracellular sequence of reactions triggered by binding
of a hormone to its membrane-bound receptor is determined
not by the hormone but rather by the properties of the cell.
Thus adrenocorticotropic hormone (ACTH) and interstitial
cell stimulating hormone (ICSH, LH) stimulate the same reaction, riz. conversion of cholesterol into pregnenolone (3-hy-
The intracellular processes are controlled by a “second
messenger”. In many cases this role is fulfilled by cyclic 3’,5’adenosine monophosphate (3’,5’-CAMP) (Fig. 3). However,
3’,5‘-CAMPcan only be produced from ATP once the enzyme
adenylate cyclase has been activated. Cuatrecasas[slhas postulated that the receptor and the enzyme initially occur separately
in the membrane. It is then the hormone-receptor complex
which combines with the enzyme and effects its activation.
Germ cells
Adrenal cortex
P regnenolone
Ald 0 s t e r one
(Mineral corticoid)
(G estagen)
- -
Referentially testicle
E s t r adiol
Referentially ovary
- - ------
Fig. 2. Hormonal stimulation of steroid production in the adrenal cortex and in the germ cells (according to ref. [7a]), ACTH, adrenocorticotropic hormone; ICSH,
interstitial cell stimulating hormone.
The fact that different end products
are formed (mainly corticoids in the adrenal cortex and mainly
androgens, estrogens, and gestagens in the germ cells) is attributable to the specific enzymatic pattern of these cells (Fig.
0’ 3,5’-cAMP
e g activation o f
various enzymes
Fig. 3. Scheme of hormone action riir a membrane bound receptor
2.3. Cytoplasmic Hormone Receptors
Binding of the hormone to a cytoplasmic (intracellular)
receptor requires that the hormone penetrates into the cell.
Whereas a simple diffusion was formerly assumed to be responsible, evidence now exists that transport into the cell is a
specific process, possibly controlled by membrane-bound prot e i n ~ [ ~The
] . hormone-receptor complex is first formed within
thecell and, after activation, can penetrate into the cell nucleus
(Fig. 4). This activation is temperature-dependent and linked
with a change in the sedimentation constant” ‘I. Several models
have been proposed to account for formation and activation
of the complex, e. g. involving allosteric processes, dimerization
of the hormone-receptor complex, and its aggregation with
other proteins. An acceptor specific for the hormone-receptor
complex is assumed to exist in the cell nucleus, which, for
example, effects synthesis of the proteins important for hormonal action via transcription and translation by switching
off a repressor.
A n g o t . Chem. Int. Ed. Enql.
Vol. I S ( 1 9 7 6 ) No. 12
UNA .'
and -[H-R1 - K
[R] = [Ro]
- [H - R]
Cell wall
- K.([Ro]-[H-R])
Fig. 4. Scheme of hormone actlon rio a cytoplasmic receptor
3. Formation of the Hormone-Receptor Complex
Studies on the formation of the hormone-receptor complex
should take into account the following theoretical and practical
3.1. Formation of the Hormone-ReceptorComplex as an Equilibrium Reaction
To understand hormone(H)-receptor(R) binding it is sufficient to consider the following two equilibria for membranebound receptors (a) and cytoplasmic (intracellular) receptors
(b) respectively:
a) Membrane-bound receptor
H + R
b) Cytoplasmic receptor
+ R T H-R
+ H-Ractivate,j
These are formation of the hormone-receptor complex H - R
(for a and b) and activation of the cyclase system (cf. Fig.
3) for (a) and temperature-dependent activation of the hormone-receptor complex (cf. Fig. 4) in case (b). Depending on
the kind of binding assay and on the experimental conditions,
either the first equilibrium only or more or less the sum
of the two equilibria will be determined.
3.2. "Direct" Determination of the Receptor Binding
If the hormone or hormone analog is present in radioactively
labeled form then its binding to the receptor is open to direct
measurement. The readily measurable concentrations of the
hormone-receptor complex (H - R) and of the free hormone
(H) are preferentially used as variables. Graphic representations of complex formation leading to straight lines are of
considerable advantage (Fig. S)[' 'I. Slope and intercepts permit
calculation of binding parameters. Most frequent use is made
d the equation reported by Scatchard"zl (cf. also Fig. 5e),
which is derived as follows:
Angew. Chem.
Fig. 5. Plot of formation of the hormone-receptor complex ( H - R). a ) [H R]=f[H]; b) [H-R]=f(log[H]):
C) log[H-R]=f(log[H]):
d) I/[HR]=f(l/[H]): e) [H-R]/[H]=f([H-R])
(plot according to Sco~chord).
In!. Ed. Engl. 1 W d . 15 ( 1 9 7 6 ) No. 12
In practice, the overall concentration of receptor [Ro] is
used instead of the generally unknown concentration of free
receptor [R]; [R,] is assumed to be proportional to the
readily measurable concentration of protein. The slope of
the straight line gives the affinity constant K, and the intercept
with the abscissa provides a measure for the number of binding
Application of the law of mass action requires that the
measurements be performed below the saturation range of
the receptor (Fig. 6). After equilibration, the free and receptor
bound hormone are separated and assayed. The receptor concentration in a preparation is normally of the order of < lo-'
mol/l. Determination of such low concentrations is only possible with hormones having specific activities of more than
10 Ci/mmol. Tritium and, in the case of proteohormones,
iodine isotopes are used in practice. The presence of one
or more tritium atoms in a molecule has hardly any effect
on its affinity for a receptor. However, incorporation of an
iodine atom, having roughly the same size as a benzene ring,
may well modify the stereochemistry and physical chemistry
of the molecule and thus impair its affinity towards the receptor. The situation is further complicated by the fact that
present in radioactively labeled form. This technique requires
a radioactively labeled reference substance. The proportion
of reference sample bound by the receptor is reduced by
the test substance (Fig. 8). This reduction of receptor binding
is termed competition. It depends upon the concentration
lest substance
- 1
Fig. 6. Schematic representation of "direct" measurement of receptor binding.
0 . hormone with high aNinity: 0, hormone with slight affinity for the receptor.
more than one amino acid may be iodinated in most proteohormones. Hence the presence of several analogs displaying various degrees of iodination, and possibly different affinities
for the receptor must be expected, together with non-iodinated
hormone. The synthesis of analogs of insulin mono-iodinated
at various sites demonstrated that these derivatives may cover
the entire spectrum from inactive to fully activel13-' 'I.
Graphical representations permit scrutenization of theoretical binding models by comparison of calculated and experimental plots. Thus a Scatchard plot in which an increase
up to a maximum precedes the linearly decreasing range indicates a cooperative effect in complex formation (Fig. 7a).
Fig. 7. Scatchard plot, a ) for cooperative binding and b) in the presence 01
two binding sites.
The Scatchard equation occasionally results in a continuous
curve. This can be attributed to the presence of more than
one binding site. Such curves can be resolved graphically" 61
or by computer iteration into two or more straight lines
(Fig. 7b). In this way two binding sites have been demonstrated
for many hormones such as insulin and prostaglandins"'. ''I.
A non-linear Scatchard curve may also arise because a
mixture of compounds having different affinities was present
instead of a homogeneous hormone. This is to be expected
primarily with iodinated p r o t e o h o r m ~ n e s*'[I. ~ ~ ~
In the "direct" measurement of receptor binding it must
be assumed that not only formation of the hormone-receptor
complex but also the second equilibrium-activation of the
cyclase system or of the cytoplasmic receptor complex-are
also monitored. The resulting apparent association constants
are then too high.
3.3. Determination of Hormone-Receptor Binding by the
Method of Competitive Protein Binding
The method of competitive protein binding must be used
if the test substance (hormone or hormone analog) is not
v -
0 -
Fig. 8. Schematic representation of competitive determination of receptor
binding. 0 . radioactively labeled reference (tracer): 0. nonradioactive test
substance (hormone)having the same affinity for the receptor as the reference
substance: 0, nonradioactive test substance (hormone) having less affinity
for the receptor than the reference substance.
of sample and upon its affinity towards the receptor. In contrast
to the "direct" determination of binding, the measurements
must be performed in the saturation range of the receptor.
After incubation, the binding sites of the receptor are saturated;
the subsequent reaction (activation of the cytoplasmic hormone-receptor complex or of the cyclase system) should therefore have no effect on the ratio in which reference substance and
the sample are bound.
The competition curves obtained for varying concentrations
of sample at constant concentration of reference substance
have a sigmoidal shape typical for protein binding. They
can be linearized within a wide range, for example by the
logit-log transformation originally developed by Rodbard for
radioimmunoassays[' (Fig. 9).
cte. [mol/Ll
c,[ m o l / l l
Fig.9.a)Competitioncurveandb) its linearization by logit-log transformation
according to R o d h d [21]. In ['XI binding/( 100- '',>binding)] = f(Iog~,~.J.
clc., = concentration of test substance.
A drawback of the method of competitive protein binding
is that the competition curves obtained for several samples
with the same receptor are ’often not parallel. The relative
affinity therefore cannot be calculated simply from these competition curves. Considerable experimental and mathematical
effort would be required. In practice, this problem is circumvented by relating arbitrarily selected points on these curves,
usually that of 50 %competition, with one another. Experience
gained with non-parallel competition curves can be confirmed
by simulation on an analog computer and by calculation
of such curves[221(Fig. 10).
The choise of tissue often depends upon the problem
to be solved. Thus the relationship between insulin and lipid
metabolism are best studied with receptors of fat cells or
ofthe liver. The choice of animal species can also be important.
For instance, considerable concentration differences could be
established for corticoid receptors[231in various species (Table
Table 2. Concentration of corticoid receptor in rat and rabbit tissue
[pmol receptor. mg protein]
Skelet,il muscle
Fig. 10. Competition curves obtained by simulation on an analog computer.
K,,, = relative association constant (given). Cf = competition factor. See
text for details.
The three curves which were calculated for relative dissociation constants (Kre,) of 0.1, 0.01, and 0.001 are not parallel.
Moreover, the concentrations determined for 50 % competition are not in the ratio I , : 10 and 1 : 100, but I :2.5 and
1 : 12.5. These values should therefore not be designated as
relative affinities. Instead the term “competition factor” (CF)
has been proposed. It is defined as the ratio ofthe concentration
of the test sample (c,,,) and that of the reference substance
(crer.)required for 502, competition :
4. Receptor Preparations
Receptor preparations are preferentially obtained from typical target organs of the respective hormone. For some hormones several kinds of tissue are suitable (Table 1).
Table I . Tissue, auitable for receptor preparations.
ACTH 1;idrenocorticotropic hormone)
Adrenal cortex
Kidney. bone. lymphocytes
Liver. pencreah. adipose tissue.
Gonadotropins :
HCG 1 human choriongonadotropin)
LH IC‘SH (interstitial cell stimulating hormone)
FSH lfollicle stimulating hormone)
Testes. ovary
Testes. ovary
Liver. adipoae tissue. lymphocytes.
Myocardium. liver. erythrocytes,
uterus. adipose tissue. brain
Frog skin, mamma, adipose tissue,
Uterus. ovary. adipose tissue, liver,
kidney, adrenal cortex. thyroid.
t hrombocytes
0 64
0 06
0 16
0 19
0 23
0 15
0 45
0 02
0 OX
0 07
0. I1
0 03
0. I 3
0. I1
0 I6
Isolation of a receptor is extremely difficult. Therefore crude
receptor preparations are frequently used. The procedure for
cytoplasmic receptors is relatively simple. The cytosol available
after homogenization of the tissue and centrifugation is
employed almost exclusively as sample preparation.
The preparation of a membrane-bound receptor offers more
variation. Reports have been published using intact discrete
cells (P.y. erythrocytes, lymphocytes) or cells liberated from
tissue by treatment with proteolytic enzymes (liver cells, fat
cells, rtc.). Use of intact cells often permits examination of
subsequent biological reactions, P. y. activation of the adenylate
cyclase system, parallel to hormone binding studies. Rather
impure membrane fractions are often employed as receptor
preparations instead of intact cells. Membrane-bound receptors have also been successfully solubilized by treatment with
preferably nonionic detergents, without significantly affecting
the binding. However, it has yet to be proved that such a
soluble hormone-receptor complex still has a biologically relevant intrinsic activity after reconstitution.
5. Receptor-Binding Assay
The receptor preparation must be incubated with the hormone under conditions ensuring stability of the receptor and
equilibrium (see Sections 3.1). Experiments with the rather
unstable soluble (cytoplasmic)receptors are usually performed
between 4 and 1 5 T , rarely at higher temperatures. Incubation
ofthe more stable membrane-bound receptors are often carried
out at room temperature, and sometimes at 37°C. Equilibrium
is generally reached within a few minutes to several hours.
Separation of free and receptor-bound hormone requires special attention; it should be performed under conditions where
dissociation of the hormone-receptor complex is minimal.
A compromise usually has to be met between optimal separation and time-saving performance.
Different separation techniques are described in the
available literature, Density differences are exploited in
separation by ultra~entrifugation[~~~~.
For larger differences
in density, r . 8 . for membrane fractions or intact whole cells,
low speed centrifugation will suffice[401.A particularly elegant
method for fat cells consists in floatation through an oil layer
of intermediate specific gravity[23b1.Separation by molecular
size can be accomplished with membrane filtersf23c1or by
gel chromatography[23d1.Charge differences are utilized in
gel electrophoresis[23e1.Separation is also possible by binding
the free hormone to adsorbents. These adsorption procedures,
specifically with dextran-coated activated charcoal, find frequent application. They d o have the drawback, however, that
the pronounced affinity of the adsorbent for the hormone
can interfere with the equilibrium. In all separations it is
advisable to work at low temperature to suppress dissociation
of the hormone-receptor complex.
Table 3. Relationship between insulin concentration in the plasma and insulin
receptor concentration (measured in various tissues) in endocrine disorders.
1. increased: 1 decreased concentration.
Obesity + Diet
Maturity-onset diabetes
Maturity-onset diabetes
+ Sulfonylurea
- ~-
normal or t
(Chinese hamster)
Corticoid excess
6. Applications of the Receptor-Binding Assay
Having discussed the theoretical and methodological principles of the receptor-binding test, its applications will now
be discussed (with the aid of selected examples).
6.1. Radioreceptor Assay as a Method of Quantitative Hormone
Like a radioimmunological assay[22a1,the radioreceptor
assay can be used for determining hormone concentrations
in tissue samples and body fluids. A hormone-specific receptor
preparation is used instead of antibodies.
Whereas a radioimmunoassay will embrace structurally
similar compounds, irrespective of their biological activity,
a radioreceptor assay will register all substances having the
hormone-specific biological activity, regardless of whether they
are structurally related to the original hormone.
The generally low stability of the receptors compared with
the immunoglobulins can be a handicap. This is particularly
true for cytoplasmic receptors; the only assay so far reported
with these receptors is one for e ~ t r a d i o l ' ~ ~
with the
more stable membrane-bound receptors have been described
for ACTH'251,g l ~ c a g o n [ ~insulin[z71,
growth hormonefz8],
and the gonadotropinsf2'- 3 1 1and prostaglandin E2[321.Based
on the receptor assay for HCG (human choriongonadotropin),
an extremely sensitive pregnancy test has been developed
which can already detect a pregnancy six to eight days after
6.2. The Receptor-Binding Assay for Characterization of Endocrine Disturbances
complex formation will be promoted by increasing the receptor
concentration[35.361. It could be shown in animals and man
that essentially normal receptor concentrations are re-established on reaching a normal insulin level after normalizing
the pathological state, e.g. by a suitable diet.
Current interest is presently focused upon assays for estrogen
receptors in cases of breast cancer (mammacarcinoma).
Approximately one half of the tumor tissue samples could
be shown to contain estrogen receptors (hormone-dependent
tumors). Tumors which are not affected by treatment with
estrogens are termed
In the case of estrogen-dependent tumors a regression can
often be achieved by treatment with antiestrogens, and less
frequently with androgens. Hormone therapy is often supported by ovarectomy, adrenalectomy, and occasionally by
hypophysectomy in order to stop production of endogenous
hormones. A regression is observed in about 60% of the
cases treated in this way. Hormone treatment and ablative
surgical measures are generally unsuccessful in the case of
autonomous tumors. Such tumors require administration of
cytostatics (Fig. 11).
Estrogen receptor in mammary tissue
Negative 50 %
Hormone treatment
ablative surgery
J \
60 %
40 %
Estrogendependent tumor
In some cases it has been possible to correlate endocrine
disorders with the receptor content of the relevant tissue.
The relationship between disturbances of carbohydrate and
lipid metabolism and the content of insulin receptors has
been studied particularly thoroughly. In the carbohydrate
and lipid metabolism of man and animals several pathological
states are characterized by an increased or diminished insulin
level in the plasma[341.The concentration of insulin receptors
measured in such cases appears to be inversely correlated
with the insulin concentration (Table 3). Thus it was deduced
that insulin itself regulates the receptor concentration. At
high insulin levels the equilibrium will be shifted strongly
in favor of receptor-complex formation. Therefore, a low
number of receptor molecules will suffice for the full biological
activity of insulin. Conversely, at low insulin concentrations
Positive 50 %
Treatment with
Autonomous tumor
Fig. I I . Treatment of a mammacarcinoma depending upon its content of
estrogen receptor
The receptor-binding assay permits classification of the tumor and thus indicates the necessary form of treatment. In
the case of autonomous tumors drastic surgery can then be
6.3. Receptor-Binding Assay to Determine Structure-Affinity
The receptor-binding assay plays an important role in studies on structure-activity relations of hormones. The principal
goal of such work, known generally as drug design, is the
Chrfri. Irrr. Ed. E r ~ g l1. &>/.15 ( 1 9 7 6 ) N o . I 2
- 1
of biological action. The search for compounds displaying
a dissociation in their action profile is therefore important.
The effect of structural modification on the binding to the
receptor has been impressively demonstrated for insulin[40-421.Various insulin analogs are bound to fat cells or liver
cell membranes to a lesser extent than the native hormone,
and the biological activity measured in citro usually also decreases. However, the maximum biological effect can always
be achieved by using a sufficiently high concentration dependent upon the particular modification. Accordingly, while the
affinity for the receptor may change on modification, the
intrinsic activity of the receptor complex does not. Studies
on insulin were facilitated by the possibility of clear-cut modification of the molecule. Removal of the N- or C-terminal
amino acid from the A chain, or of a C-terminal penta- or
octapeptide from the B chain leads to a distinct loss of affinity.
In contrast, removal of the N-terminal amino acid from the
B chain is well tolerated (Fig. 12).
$A ' - '
' t
Phe - LYS-Ah
Cleavage Cleavage
Octa- Pentapeptide
Fig. 12. Structural modification of insulin
development of active compounds superior to the native hormone. Potentially interesting compounds are those having
enhanced activity, which can be achieved by a higher concentration at the site of action, by a higher affinity for the receptor,
or by raising the intrinsic activity of the hormone-receptor
complex (cf. Fig. 1). Many hormones have a broad spectrum
Cortexolone, C F = 3
Corticosterone, C F = 1
Cortisone, C F = 1 2 0
Cortisol, C F = 1
Prednisolone, C F = 0.3
c H,
C F = 0.08
C F = 0.11
C F = 0.17
Fluocortolone-2 1 - a c e t a t e ,
C F = 0.10
Fig. 13. Binding of glucocorticoids to the receptor (rat thymus). C F = competition factor (see
Section 3.3).
Angen'. Chrm. 117t. Ed. Engl.
1 Val. 15
( 1 9 7 6 ) No. 12
Substitution of the terminal amino groups or introduction
of intramolecular bridges reduces the affinity, but it is not
lost entirely. Many of these derivatives nevertheless lead to
a pronounced reduction of blood sugar levels irr r i m This
effect is attributed to the enhanced resistance of the modified
molecule towards enzymatic degradation in the liver.
The receptor binding of glucocorticoids will serve as a
further example (Fig. 1 3)[431.Starting from cortisol, loss of
the 11p-hydroxyl group (cortexolone) but not of the 17%-hydroxyl group (corticosterone) reduces hormone binding. Oxidation to the 11-ketone (cortisone)strongly impairs its affinity.
The biological activity still observed for I 1 -ox0 corticoids
is attributable to their in riro reduction to the 1 t-hydroxy
derivative. Introduction of 1,2-double bond (prednisolone)
enhances the affinity towards the receptor. The biological
activity also increases. Glucocorticoids exhibiting even
stronger binding to the. receptor are obtained by introduction
of fluorine atoms into the 9%or 6 1 position. A methyl group
in the 16a position also has a favorable effect. Esterification
of the 21-hydroxyl function with a short-chain carboxylic
acid has practically no effect on binding. Only upon esterification with the longer valeric acid is binding reduced.
Pregnadiene-2 I -carboxylic esters'441 represent a new class
of glucocorticoids. They exhibit moderate to good binding,
irrespective of the chain length of the alcohol component.
In spite of this affinity, the derivatives are ineffective in all
systemic inflammation tests. The reason is to be found in
their fast hydrolysis to the free acid which is devoid of receptor
affinity (Fig. 14).
R e v e r s i b l e binding
to r e c e p t o r
No binding
to r e c e p t o r
I A 138.141
Fig. 14. Locally active c o r t i c o ~ dwith a labile bond designed to prevent
systemic activity.
These compounds deserve considerable interest as local
anti-inflammatory agents having practically no systemic sideeffects.
7. Outlook
Numerous aspects of hormone-receptor interaction have
been investigated since the description of the first receptor
protein. However, there still remain many unanswered questions concerning, for example, isolation and characterization
of receptor proteins, their amino acid sequence and conformation, and the structure of the receptor molecule a s an integral
component of the cell membrane. Little is also known about
the mechanism of receptor-controlled gene expression and
the regulation of receptor biosynthesis.
New findings in all these areas will further our knowledge
of hormone action.
Received: July 4. 1976 [A 138 I€]
German version: Angew. Chem. XX. 7YO (19761
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