British Medical Bulletin (1981) Vol. 37, No. 3, pp. 281-285
ENDOCRINOLOGICAL CONTROL OF GROWTH AT PUBERTY C G D Brook
to express testicular size. The spurt in height and other
dimensions begins in boys about one year after testicular
enlargement and reaches its maximum about a year after this,
on average at about the age of 14.0 years. In girls, the height
spurt often begins as soon as the breast development, and
sometimes even before, and it is only when the peak of the height
spurt has been passed that menarche occurs. For a general
account of these changes the reader is referred to Marshall
(1981).
ENDOCRINOLOGICAL CONTROL OF
GROWTH AT PUBERTY
C G D BROOK MA MD FRCP DCH
The Middlesex Hospital, London
1
Puberty is defined here as the period in which reproductive
capacity is attained. As such it is rather different from
adolescence, which is the whole period of growing up from
childhood to adulthood and extends for much longer than the
events of puberty. The physical manifestations of puberty,
specifically the secondary sex characteristics, begin to appear by
the 1 lth birthday in 50% of girls and by 11$ in 50% of boys.
The usual first manifestation of female puberty, enlargement of
the breasts, is much more visible than the first manifestation of
male puberty, enlargement of the testes, which perhaps has
given rise to the common notion that girls have a greater
advancement over boys than this. Because the height spurt
associated with female puberty comes early in the sequence of
events, whilst the height spurt associated with male puberty
comes late, there is a difference of two years in this manifestation of puberty.
The timing of the onset of puberty is under both genetic and
environmental control. Monozygotic twins show a mean
difference in menarcheal age of only two months, while
dizygotic twins show a difference of eight months (TiserandPerrier, 1953). Such data have to be interpreted with caution in
that monozygotic twins are usually treated in a much more
similar fashion than dizygotic ones, and answers from twin
studies, or even from mother-daughter correlations, may be
misleading because of this (Hawk & 3rook, 1979). What is
needed is for the children of parents followed up in one of the
longitudinal growth studies to be followed through their own
pubertal development
The course of puberty varies greatly, not only in timing but
also in duration. For example, 50% of girls take four years to
go through all stages of puberty but a few may take only 18
months and a few longer than five years. The timing of the
onset of puberty does not seem in any way to presage the
duration of pubertal change.
By comparison, the sequence of events is much less variable.
It will be assumed, for the purposes of this paper, that the reader
is familiar with the well-defined stages through which male
genitalia, female breasts and pubic hair in both sexes pass
(Tanner, 1962) and with the measurement of testicular volume
281
Downloaded from http://bmb.oxfordjournals.org/ at Pennsylvania State University on May 17, 2016
After the very active endocrine events in fetal life and the first
months after birth, there is a period of relative quiescence during
the pre-school years. Nevertheless, the gonads, certainly in
girls, are not totally inactive, as was previously thought, and
cycles in ovarian follicular development, of very low amplitude
and long periodicity, do occur. It may perhaps be the
exaggeration of these cycles that leads to the cases of clinical
early puberty, especially to isolated breast development, in some
girls. Nevertheless, the first generally accepted and well-defined
endocrine event of puberty is the increase in adrenal androgen
production.
Between the ages of five and eight years in both sexes, there is
an increase in adrenal androgen production, which has most
often been registered as an increase of dehydroepiandrosterone
sulphate in the blood. It can also be detected in increases of, for
example, plasma progesterone, 17-hydroxyprogesterone and
androstenedione, and of the urinary metabolites of these
steroids. Since patients who lack adrenal glands (congenital
adrenal hypoplasia) seem invariably to have gonadotropin
deficiency (Hay, 1977) and since patients with congenital
adrenal hyperplasia and excessive adrenal androgen production
sometimes go early into puberty if they are untreated, it might be
thought that adrenal androgen secretion plays a necessary part
as preliminary to the gonadotropic events of true puberty
(Cutler & Loriaux, 1980). Yet in most children with Addison's
disease, pubertal development is normal (Lucky et al. 1977) and
premature adrenarche does not seem to be associated with
precocious puberty (Styne & Grumbach, 1978). At present
adrenarche is a definable endocrine event without an obvious
function.
Because of the possible role of the adrenal androgens in
triggering the hypothalamo-pituitary-gonadal axis at puberty
(Ducharme et al. 1976), a case has been made for a separate
adrenal androgen-stimulating hormone originating from the
pituitary gland (Parker & Odell, 1979). On the other hand,
changes in adrenal steroid secretion induced by adrenocorticotropic hormone (ACTH) infusion during puberty (Genazzani et
al. 1979) in no way exclude ACTH itself from being the
regulator of adrenal androgen secretion. A possible mechanism
could be that a small change in cortisol responsiveness to
ACTH allows an increased amount of steroid precursors
incorporated into the zona fasiculata and zona reticularis to be
metabolized to adrenal androgens. An ACTH-related peptide
might be another candidate for such a role and one curious fact,
which has not so far been explained, is the rise of blood-pressure
levels that occurs at the same time as adrenarche (National
Heart, Lung, and Blood Institute's Task Force on Blood
Pressure Control in Children, 1977). The juxtaposition in time
of these two phenomena may well be worthy of further study.
The evidence for an adrenal androgen-stimulating hormone rests
on the fact that bovine pituitary extract infused intravenously
1 An endocrinological overview
2 Secondary sex characteristics
3 The adolescent growth spurt: changes in body size and
shape
4 Changes in body fat and muscle
5 Strength, exercise tolerance and other physiological
functions
6 Conclusion
References
Vol. 37 No. 3
An Endocrlnologkal Overview
ENDOCRINOLOGICAL CONTROL OF GROWTH AT PUBERTY
small pulses of GnRH are certainly effective in inducing puberty
in infantile female monkeys (Knobil, 1980), and alterations in
the strength and periodicity of the stimulus alter gonadotropin
responses. A maturation of GnRH secretion seems more
probable than the gonadostat and fits better the evidence
available.
The proper functioning of the rest of the endocrine system is
also important for the normal completion of puberty. Growth
hormone and thyroxine are crucial, but there are many other
hormones which also must have important roles. Amongst
these parathyroid hormone secretion, which must be important
to the maintenance of skeletal development, has received little
attention. Prolactin concentrations increase with advancing
puberty, although not very strikingly. Whether prolactin has a
role in puberty is as yet unclear, but it might not be a direct one.
The stimulatory action of prolactin on the renal part of vitamin
D metabolism and the presence of prolactin receptors in the
adrenal cortex are challenging facts which have yet to be
explained.
Finally, the possibility that the endocrine events of puberty
are suppressed by an inhibitor, rather in the way that prolactin
secretion is suppressed by dopaminergic drugs, has also received
attention. The pineal gland secretes melatonin, which inhibits
the development of the gonads in some animals (Wurtman &
Moskowitz, 1977), so the suggestion has been made that human
puberty could be induced by a cessation of melatonin secretion.
The data in this respect are contradictory in that one study
showed just such an effect (Silman et al. 1979) while another
found no changes (Lenko et al. 19801); further studies (Fideleff
et al. 1976; Weinberg et al. 1980) failed to identify an inhibitory
effect of melatonin on gonadotropin secretion. At present tonic
inhibition of puberty remains conjectural.
2
Secondary Sex Characteristics
The gonadal steroids are primarily responsible for the
development of the secondary sex characteristics. If the
hypothalamo-pituitary-gonadal axis is in any way dysfunctional, a failure of the development of secondary sex
characteristics always occurs.
In the male, testosterone is responsible for the growth of the
penis, prostate and seminal vesicles. Experience from male
pseudo-hermaphrodites with steroid 5a-reductase deficiency
(Imperato-McGinley et al. 1974) suggests that testosterone
itself, rather than dihydrotestosterone, is the relevant hormone
at this stage of development Whether males with steroid
5a-reductase deficiency can be fertile is not clear. If they are
not, it may be because dihydrotestosterone is important for
spermatogenesis.
The generation of testosterone and the enlargement of the
testes, which are characteristic of early puberty, seem to be due
to LH and FSH secretion. There is some evidence to suggest
that the bioactivity of LH secreted in puberty increases
more than the immunoreactivity would suggest (Lucky et al.
1980). This is important because it has always been rather
puzzling that testosterone first appears at a time when FSH
immunoreactivity shows an earlier and greater increase than
LH. The size of the testes is probably largely the result of
seminiferous tubular enlargement, which is under FSH control.
The development of body hair has received rather little
1
Lcnko H L, Lang U, Aubert M L, Paunter L & Sizoncnko P C (1980) Communication
to the European Society of Paediatric Endocrinology, Bergamo.
282
Br. Med. Bull. 1981
Downloaded from http://bmb.oxfordjournals.org/ at Pennsylvania State University on May 17, 2016
into the dog produces a greater rise in adrenal androgens for a
given rise in cortisol than does ACTH (Parker & Odell, 1979).
Interpretation of this finding is, as Cutler & Loriaux (1980)
point out, difficult since neither the dog nor the cow undergoes
an adrenarche similar to man.
The role of the gonadotropins in maintaining reproductive
function in adult life is not in question. In the adult male,
luteinizing hormone (LH) promotes secretion of testosterone
from the Leydig cells and testosterone exerts a negative
feedback on pituitary release of LH. Follicle-stimulating
hormone (FSH) causes maturation of the seminiferous tubules
and spermatogenesis, and feedback is believed to be exerted by a
hormone called inhibin. In the female, LH may be responsible
for initiating steroidogenesis in the ovarian follicle, but FSH is
certainly responsible for aromatization and the release of
oestradiol. During the maturation of the female hypothalamopituitary axis the pituitary becomes sensitive to positive
feedback; thus increasing concentrations of oestradiol cause
release of LH in mid-cycle. What actually initiates the LH peak
is still not clear: it probably involves a small fall in oestradiol
concentration, causing both LH and FSH to be secreted
simultaneously.
The way in which the prepubertal child develops this control
system is controversial. All available evidence suggests that
there is one hypothalamic gonadotropin-releasing hormone
(GnRH) that is responsible for the stimulation of secretion of
both LH and FSH by the pituitary gland. This decapeptide is
available as a pharmacological stimulus of gonadotropin
secretion and much experience has been gained with it. As it
has been hard to establish reliable assays for GnRH in the
peripheral circulation, it is difficult to be quite sure of its mode
of secretion in the normal adult human, but it is believed to be
produced episodically, not cyclically; thus a relatively constant
stimulus is applied to the pituitary gland and the pattern of
gonadotropin response which can be measured in adult humans
results from the feedback mechanisms at a pituitary level.
Recent experience with GnRH as a therapeutic substance has
shown that in large amounts there may be down-regulation of
gonadotropin secretion (Brook & Dombey, 1979) and that
gonadotropin secretion can be maintained only by small pulses
of GnRH (Crowley & McArthur, 1980).
This situation, which may be reasonably clear in the adult, is
anything but clear in the child. Based on studies in normal
individuals (Styne & Grumbach, 1978) and on agonadal
patients (Conte et al. 1980), it has been suggested that there
exists a "gonadostat" with a progressively lowering threshold to
account for puberty. The problem here is that the concept
applies so very much better to LH secretion than it does to FSH
secretion and the variation between individuals is very large.
Our experience (C G D Brook and M A Preece, unpublished
data) is that the variation of responsiveness of gonadotropin
secretion to GnRH infusion increases with advancing age and
state of puberty but that an absolute progression of response is
not seen. These findings are not at odds with the data of Styne
& Grumbach but they alter the interpretation that has been
placed on the latter.
In the absence of large longitudinal studies, the concept of a
lowering of a gonadostatic mechanism to enable the same
concentration of GnRH to produce increasing amounts of
gonadotropins seems without a secure foundation. More
probable seems a gradual change in the periodicity of secretion
of pulses of GnRH, leading to an alteration in over-all patterns
of gonadotropin secretion during the 24-hour period. Frequent
C G D Brook
ENDOCRINOLOGICAL CONTROL OF GROWTH AT PUBERTY
3
The Adolescent Growth Spurt: Changes in Body Size and
Shape
The adolescent growth spurt results from synergism between
gonadal sex steroids and growth hormone, as long as other
endocrine functions are normal. The part played by adrenal
androgens, particularly in females, is disputed. It is extremely
baffling why the height spurt of female puberty comes early in
the sequence of pubertal development, while the height spurt in
males comes late. It is important because the additional height
gained during the whole of the height spurt (about 28 cm in boys
and 25 cm in girls) is quite insufficient to explain the final
difference in heights between the sexes and must, therefore, be
due to the time when the take-off of the height spurt occurs. A
loss of two years of growth at a prepubertal rate in females and
the fact that the peak of the adolescent growth spurt is rather
greater in males accounts for the difference in adult height
between men and women. More of the spurt in height comes
from acceleration in trunk length than from acceleration in the
growth of the legs.
The sex steroids seem to be primarily responsible for the
changes in the vertebral column and in the width of the
shoulders and hips (Aynsley-Green et al. 1976; Tanner et al.
1976; Laron et al. 1980). Growth of these parts occurs even
when growth hormone is absent and is reduced by only about
one-third. Conversely, growth of the legs is largely growth
hormone dependent and a lack of sex steroids makes little
difference to leg length. Thus an untreated patient with isolated
283
Downloaded from http://bmb.oxfordjournals.org/ at Pennsylvania State University on May 17, 2016
administered to induce breast development As the adrenal
glands are the only source of androgens in the female, it has to
be presumed that pubic and axillary hair in females is due to
adrenal androgen secretion but that oestrogens facilitate the
receptor mechanism. It is certainly true that in pathological
conditions with excessive adrenal androgen secretion, women
can become extremely hirsute. In some patients hirsutism can
be reduced by administration of dexamethasone, suggesting that
it may be ACTH driven, and a recent paper has indicated that
cimetidine may occupy androgen receptor sites and could
perhaps be useful in this respect (Vigersky et al. 1980).
From the endocrinological point of view, menarche is
relatively unimportant It represents only that time when the
concentrations of oestradiol are such as to cause sufficient
endometrial hyperplasia that it becomes unstable when the
concentrations fall. Anovulatory cycles are the rule in puberty
in girls, which is why the duration of the cycles varies, why
bleeding is sometimes intermittent and why dysmenorrhoea is
extremely uncommon. When positive feedback causes the LH
surge in mid-cycle and ovulation results, cycles become more
regular in length and dysmenorrhoea may become a problem.
The duration of anovulatory cycles after menarche is probably
about two years, judging by postmenarcheal cycle length
(Billewicz et al. 1980).
Spermatogenesis seems to start almost as soon as the
testicular enlargement begins, to judge from the finding of
spermaturia in specimens voided in early morning in pubertal
boys (Richardson & Short, 1978). Spontaneous ejaculation of
seminal fluid occurs about a year after the beginning of puberty
and seminal fluid expressed at this time certainly does contain
spermatozoa, although in smaller numbers than in later
development. It is more difficult to assess prospects for fertility
in males than it is for females in whom biochemical changes
associated with ovulation can be measured.
attention hitherto. Pubic hair appears concurrently with the
growth of the penis, but axillary hair appears only when pubic
hair is relatively well advanced. Facial hair in males appears
later and hair elsewhere on the body, conspicuously on the
chest, appears later still. This means that the hair follicles
cannot just be unequally sensitive to differences in testosterone
level, since maximal levels are reached long before body hair
starts to appear in any amount There must, therefore, be
sequential maturation of testosterone receptors. As it is now
becoming clear that the generation of receptors is at least as
important as the secrection of a hormone, the example of the
sequence of secondary sex hair deserves some study. (It might
also be relevant to the very difficult problem of hirsutism in
females.)
Breast development occurs in both sexes at puberty. The
diameter of the areola, which is equal in both sexes before
puberty, increases rapidly, doubling in diameter in boys and
tripling in girls. Marked breast development occurs in a
substantial proportion of boys during puberty. In the large
majority of these it regresses spontaneously. When it fails to do
so, it can be a cause of great distress but is easily removed by
subareolar mastectomy. In girls breast development seems to be
a sensitive bioassay of oestradiol secretion. Occasionally, breast
development begins in the very young girl and it must be
presumed that this premature thelarche results from premature
synthesis of oestradiol receptors, so that even tne very small
amounts of oestradiol that are circulating in the pre-school
child are sufficient to bring about breast development. Again,
the measurement of receptors in breast tissue has been little
studied.
Given that testosterone can certainly be aromatized to
oestradiol at tissue level in boys, it is curious why more boys do
not develop breasts at puberty and why they regress. It has to
be presumed that testosterone itself exerts some inhibiting
activity on breast development, perhaps directly or perhaps by
influencing aromatization. Males given large doses of oestrogens, for example for carcinoma of the prostate, certainly
develop breasts and, after gonadectomy in the adult male,
gynaecomastia becomes prominent unless testosterone replacement is adequate.
There has been some discussion about whether prolactin
plays a part in the development of the pubertal breast Broadly
speaking, prolactin levels change remarkably little during
puberty on a cross-sectional basis (Franks & Brook, 1976), but
longitudinal studies do suggest a slight increment in parallel with
the increase in oestradiol (Apter et al. 1978). Given that
cosmetically normal breasts can be induced by oestradiol
therapy alone in patients with hypopituitarism, it seems that
prolactin plays little part in pubertal breast development
Oestradiol is also responsible for promoting growth of the
uterus and vagina and for the development of the accessory
vaginal exocrine glands. It is responsible for the thinning of the
vaginal epithelium and the reduction in the glycogen present.
The pH of the vaginal contents fairly accurately reflects
oestradiol secretion. These changes in exocrine secretion are
paralleled by the secretion of apocrine sweat, so that a vaginal
discharge and adult axillary sweat are often the first signs of
female puberty.
The explanation of body hair in girls is difficult In patients
with gonadal dysgenesis, at least in those with the chromosomal abnormality of the Turner syndrome, pubic hair appears
spontaneously in about 70% (Brook et al. 1974). In such
patients a rapid increase in pubic hair occurs when oestradiol is
Vol. 37 No. 3
C G D Brook
ENDOCRINOLOGICAL CONTROL OF GROWTH AT PUBERTY
sex steroids, and it is hard to exclude insulin and other growth
factors as causes. Insulinopenia is certainly associated with
poor growth and hyperinsulinism can result in acceleration in
growth. The fact that obese children tend to be tall could be
ascribed to insulin secretion, were it not characteristic that the
tall stature of these children is seen only in those who have
become obese in the early months of life when the programming
of growth seems likely to take place. Thyroid hormones do not
seem to play a part in any of these changes, unless their
secretion is pathological, when changes in body size and shape
certainly do take place.
5
Strength, Exercise Tolerance and Other Physiological
Function*
As the muscles increase in size they also increase in strength.
As this increase is so much greater in boys than in girls and as it
seems to be induced in athletes by the administration of
androgens, it is presumed that it is a direct response to
testosterone. The age-related rise in blood pressure cannot be
simply testosterone related, since the rise begins before
testosterone secretion starts, around the time when adrenal
androgens start to increase. Heart size and exercise tolerance
must be affected by these interrelations, but the latter is also
affected by haemopoietic changes. Haemoglobin concentration
in the blood is modulated by erythropoietin, and to some extent
this must be androgen dependent, as evidenced by the effect of
testosterone on patients with aplastic anaemia.
The reticulo-endothelial system in general and the lymph
glands and thymus in particular are the only structures which do
not show an adolescent spurt in growth; indeed the lymphatic
tissue reaches a peak around the age of 6-8 years and then
actually decreases during adolescence. There seems to be no
sexual dimorphism in these changes but, given the complexity
of the thymic humoral system which is now becoming evident, it
would be unwise to deny that these changes may also have an
endocrinological basis.
Changes in Body Fat and Muscle
Striking changes in body composition occur with the increase
in sex hormones and the maturation of secondary sex
characteristics during puberty. Lean body mass, skeletal mass
and body fat are approximately equal in young boys and girls
but, by maturity, men have 1^ times the lean body mass and 1^
times the skeletal mass of women whereas women have twice as
much body fat as men. These changes are difficult to relate to
the endocrinological control of pubertal developments, because
many of the changes antedate puberty by some years.
Body fat, for example, increases rapidly during the first years
of life and then declines during the subsequent five years. Sex
differences are already apparent at this time. In both sexes fat
then begins to increase and this can have little to do with
pubertal endocrinology, unless adrenal androgens are responsible. In boys, but only in boys, there is a prepubertal fat spurt
which occasionally becomes so marked as to develop into
clinical obesity. During subsequent puberty there is a shift in
body fat distribution, such that the triceps skinfold thickness
actually reduces as male puberty is completed, whilst the
subscapular skinfold increases. In girls there is a general
increase in body fat.
Given that the administration of oestrogens to males (or their
castration) leads to a feminine pattern of fat development, it
seems that endogenous testosterone secretion must be responsible for the prevention of a female pattern of fat deposition.
Patterns of fat accumulation certainly change with advancing
age, but middle-aged spread probably has more to do with
affluence than with diminishing testosterone secretion, which it
antedates by some years. On the other hand, the loss of fat in
both sexes in the seventh and eighth decades could have this
endocrine explanation.
It seems unlikely that these changes in body composition are
entirely mediated by growth hormone, somatomedins and the
6
Conclusion
It will be clear from this review that the endocrinological
control of growth at puberty is immensely complicated.
Although the sex steroids must necessarily be regarded as the
most important modulators of growth at this time, the other
hormones must be secreted in parallel with them for normal
growth to be achieved. We are beginning to learn a little about
what controls the secretion of hormones, but this is far from
understanding how they exert their effects. It is known that only
free hormones in the blood are active and the changes of
free-hormone concentrations have been very little examined to
date. Free hormones can be effective only whilst they remain in
the blood, so that catabolism of hormones, which has also
received scant attention, may be important for regulating the
growth process. Finally, now that assays are becoming
available, we have begun to learn the importance of hormone
receptors in controlling the actions of hormones. When we
understand the interaction of these complex processes, we may
approach an understanding of the endocrinological control of
growth at puberty.
284
Br. Mat. Bull. 1981
Downloaded from http://bmb.oxfordjournals.org/ at Pennsylvania State University on May 17, 2016
growth hormone deficiency has a relatively long trunk with short
limbs, whereas the gonadotropin-deficient patient has long legs.
Excessive long-leggedness may result from long continued
responsiveness to growth hormone in the absence of the
epiphyseal maturing action of sex steroids. Thus in patients,
especially males, with diminished gonadal secretion the legs may
be absolutely longer than in normal males as well as long in
proportion.
There remains much in the changes in body size and shape
which we still do not understand. It is much more a question of
why certain events do not happen in both sexes, rather than why
they happen in one. Breast development is one such event; hip
widening is another. Why is the male pelvis effectively
prevented from becoming so in spite of reasonable levels of
circulating oestradiol? The answers to these questions remain
obscure. Androgen-dependent changes (shoulder width and
body hair, for example) are more obviously confined to males.
Enlargement of the larynx, cricothyroid cartilage and laryngeal muscles, which leads to the breaking of the voice at about
13—14 years and the acquisition of an adult male voice by about
15-16 years, must be due to testosterone secretion. Nevertheless, it is said by singers that modification of the female voice
continues over a much longer period; the endocrine control of
this is again difficult to explain in the context of an early
adolescent growth spurt in females.
4
C G D Brook
ENDOCRINOLOGICAL CONTROL OF GROWTH AT PUBERTY C G D Brook
REFERENCES
Vol. 37 No. 3
285
Downloaded from http://bmb.oxfordjournals.org/ at Pennsylvania State University on May 17, 2016
Lucky A W, Rebar R W, Blizzard R M & Goren E M (1977) J. Clin.
Endocrinol. Metab. 35,673-678
Lucky A W, Rich B H, Rosenfield R L, Fang V S & Roch-Bender N (1980)
J.
Pediatr.91,205-2\3
Marshall W A (1981) In: Brook C G D, ed. Clinical paedlatric endocrinology, pp. 193-206. Blackwell Scientific Publications, Oxford
National Heart, Lung, and Blood Institute's Task Force on Blood Pressure
Control in Children (1977) Pediatrics, 59, suppl. to no. 5, pp. 797-820
Parker L N & Odell W D (1979)^m./. Physiol. 236, E616-E620
Richardson D W & Short R V (1978)/. Biosoc. Set. suppL 5, pp. 15-25
Silman R E, Leone R M, Hooper R J L & Preece M A (1979) Nature
(London) 282,301-303
Styne D M & Grumbach M M (1978) In: Yen S S C & Jaffe R B, ed.
Reproductive endocrinology: physiology, palhophysiology and clinical
management, pp. 189-240. Saunders, Philadelphia, PA
Tanner J M (1962) Growth at adolescence, 2nd ed. Blackwell Scientific
Publications, Oxford
Tanner J M, Whitehouse R H, Hughes P C R & Carter B S (1976)/. Pediatr.
89, 1000-1008
Tiserand-Perrier M (1953)/. Genet. Hum. 2,87-102
Vigersky R A, Mehlman I, Glass A R & Smith C E (1980) New Engl. / . Med.
303, 1042
Weinberg U, Weitzman E D, Fukushima D K, Cancel G F & RosenfeW R S
(1980)/. Clin. Endocrinol. Metab. 51, 161-162
Wurtman R J & Moskowitz M A (1977) New Engl. / . Med. 296, 1329-1333,
1383-1386
Apter D, Pakarinen A & VOiko R (1978) Acta Paediatr. Scand. 67,417^423
Aynsley-Green A, Zachmann M & Prader A (1976) / . Pediatr. 89, 9 9 2 999
Billewicz W Z, Fellowei H M & Thomson A M (1980) Ann. Hum. Blol. 7,
177-180
Brook C G D & Dombey S (1979) Clin. Endocrinol. 11,81-87
Brook C G D, MQrset G, Zachmann M & Prader A (1974) Arch. Dis.
Child. 39,789-795
Conte F A, Grumbach M M, Kaplan S L & Reher E 0 (1980) / . Clin.
Endocrinol. Metab. 50,163-168
Crowley W F 4 McArthur J (1980)7. Clin. Endocrinol. Metab. 51,173-175
Cutler G B & Loriaux D L (1980) Fed. Proc. 39,2384-2390
Ducharme J-R, Forest M G, De Peretti E, Sempe R & Bertramt J (1976) / .
Clin. Endocrinol. Metab. 42,468-^476
FidelefT H, Aparicio N J, Guitelman A, Debe(juk L, Mancini A & Cramer C
(1976)/. Clin. Endocrinol. Metab. 43,1014-1017
Franks S & Brook C G D (1976) Harm. Res. 7,65-76
Genazzani A R, Pintor C, Facchinetti F, Inaudi P, Maci D & Corda R (1979)
J. SteroidBiochem. 11,571-577
Hawk L J & Brook C G D (1979) Arch. Dis. Child. 54,877-879
Hay I D (1977)Lancet, 2,1360-1361
imperato-McGinley J, Guerrero L, Gautier T &. Peterson R E (1974) Science
(New York) 186,1213-1215
Knobil E (1980) Recent Prog. Horm. Res. 36,53-88
Laron Z, Roitman A & Kauli R (1980) Clin. Endocrinol. 10,393-399
BRITISH MEDICAL BULLETIN
1981
VOL. 37
No. 3
PROGRESS IN OESTROGEN RESEARCH
A joint meeting entitled 'Oestrogens 1980' was held at the Institute of Education,
London, on 25 November 1980 by the Society of Endocrinology, the Section of
Endocrinology of the Royal Society of Medicine and the Medical and Scientific
Section of the British Diabetic Association.
Papers were presented by the following speakers:
J. FISHMAN
J. S. PATTERSON
R. B. HEAP
J. B. BROWN
A. B. M. ANDERSON
P. SIITERI
B. E. C. NORDIN
Downloaded from http://bmb.oxfordjournals.org/ at Pennsylvania State University on May 17, 2016
S. G. HILLIER
B. R. BHAVNANI
H. J. VAN DER MOLEN
J. H. CLARK
K. D. M A C R A E
The papers have been published as the supplement, Progress in Oestrogen Research,
which was distributed to all subscribers to The Journal of Endocrinology. The
publication is also available for purchase as a separate item, price £15.00. Orders
accompanied by cheques made out to 'Journal of Endocrinology Ltd' should be sent
to the Biochemical Society (Publications), P.O. Box 32, Commerce Way,
Colchester, CO2 8HP, Essex.
THE JOURNAL OF ENDOCRINOLOGY
The scope of The Journal of Endocrinology covers the general, comparative and
clinical branches of the subject, including the anatomy, biochemistry and physiology of reproduction, endocrine chemistry, neuroendocrinology and the influence
of hormones on behaviour.
At a time when the increasing complexity of the subject causes narrow specialization, The Journal of Endocrinology maintains a broad coverage of its field. By
publishing the best work of common interest to investigators using widely disparate
techniques, The Journal of Endocrinology provides a forum for biologists,
biochemists and clinicians.
Subscription Rate (1981)
1 year (4 volumes, each of 3 parts)
£90.00
Per volume
£23.00
Per part
£8,00
U.S.S205.00
U.S.S52.00
U.S.S18.00
Orders and subscriptions should be sent to the Biochemical Society (Publications),
P.O. Box 32, Commerce Way, Colchester, CO2 8HP, Essex.
286
Br.Med.Bull. 1981