We had to wait until the middle of this century before Kappersā€™ classic
studies mapped out the complex neural link between this gland and the visual
system in mammals. By now, quite a number of biologists were intrigued.
Studies of pineal tumours in humans at the turn of the century had shown a
link to reproduction: a common feature of pineal tumours is precocious
puberty, while comparative anatomists had shown that the pineal gland bore a
remarkable resemblance to the parietal gland (commonly known as the ā€œthird
eyeā€) of lizards. It became clear that there was a strong evolutionary theme
in all vertebrates linking the pineal and various photosensory organs.

Then, in the early 1950s, Aaron Lerner at Yale University embarked on a
strange quest. He knew that a substance produced by the pineal gland caused
skin lightening in frogs (and also many fish). Extracts from the pineal glands
of cattle caused a dramatic change of pigment distribution in cultured frog
skin cells (melanophores) and Lerner wanted to find a factor in humans which
might be useful. The task was immense, requiring years of effort and enormous
care in the biochemical purification of melatonin. In 1958 he published a
paper in the Journal of the American Chemical Society entitled: ā€œIsolation of
melatonin: pineal factor that lightens melanocytesā€.

The hormone he had described was a fat-soluble indoleamine which he called
melatonin after the frog melanophore. (Reputedly, he nearly called it ā€œYalinā€
in honour of his university.) He could surely never have anticipated the
extraordinary impact that this seemingly obscure study was to have on
neuroscience and endocrinology during the next 40 years. Melatonin is now the
worldā€™s most fashionable hormone and is the subject of this quite superb book
by Josephine Arendt, Melatonin and the Mammalian Pineal Gland.

We now know that in mammals melatonin doesnā€™t control skin pigmentation,
but is part of the biological clock mechanism, providing the brain with a cue
that measures the passage of time. The pineal gland and its hormone melatonin
is regulated by a circadian clock (located elsewhere in the brain), so levels
are produced rhythmically with high concentrations at night and low during the
day. Melatonin is the hormone of the night and, as night length varies, so
does the duration of this nocturnal signal. In seasonally breeding mammals,
such as sheep and deer, an extraordinary array of physiological cycles,
including reproduction (the gonads regress back to the pre-pubertal state in
the nonbreeding season), sexual behaviour, appetite level and fattening and
coat moult, are regulated by the changing pattern of daily melatonin secretion
over the course of the seasons. It is also involved in the timing of
hibernation. In this respect, the hormone is the nearest we have to ā€œchemical
³Ł¾±³¾±šā€.

As melatonin is also known to play an important role in integrating
circadian rhythms, some researchers have been describing it as ā€œcircadian
glueā€. Studies of rodents show that the fetus maintains circadian synchrony
with the mother by virtue of a maternal melatonin signal which crosses the
placenta and entrains the circadian clock of the fetus in its darkened
world.

So, what of humans? There is good evidence that melatonin can help to reset
our own daily rhythms when taken at the appropriate phase of the circadian
clock. This has been developed by Arendt and others as a possible treatment
for jet-lag. It also has an important application in synchronising sleep-wake
cycles in blind people who, lacking the entraining influence of the light-dark
cycle, often ā€œfree-runā€ so that for long periods of time they are going to
work in the middle of their own biological night. Arendtā€™s work has shown that
melatonin may help to synchronise such people.

Applications to human medicine and the control of biological rhythms are
clearly only in their infancy. The cloning of clock genes and defining the
action of melatonin at the molecular level remains a target for researchers,
but most anticipate these kind of studies will lead to a new pharmacology of
clock biology. This may include understanding the physiological basis of the
control of sleep-wake cycles and perhaps tackling the problem of sleep rhythm
disturbance in the elderly and the severe physiological and psychological
disruption associated with shift work.

Unfortunately, the media are now in the grip of what a recent review
article in the journal Cell describes as ā€œMelatonin Madnessā€. The twin
American fears of cancer and ageing have been pandered to in a book on the US
bestseller list which proposes melatonin as a cure for both. A reliable source
has it that last year in California (where else?), melatonin topped aspirin
sales. In the US, clinicians have prescribed enormous pharmacological doses of
the hormone for a bewildering array of ills, while others have developed the
idea that bright lights which lower the levels of melatonin in the body might
be used to cure the psychiatric illness of seasonal affective disorder. I find
this a great pity because it will inevitably raise unreasonable expectations
in what is an important and fast-developing field.

Arendtā€™s book is the first comprehensive treatment of melatonin and so is
very welcome. Melatonin and the Mammalian Pineal Gland is also timely because
it has such an extensive and interesting discussion of the science of human
biological clocks. Her own credentials are impeccable as she played a key part
in developing robust radioimmunoassays for the measurement of melatonin and
its metabolites and studied the biological action of melatonin on humans. This
even included a study of rhythms of people working in Antarctica for the
British Antarctic Survey throughout the long winter of permanent darkness.

Melatonin and the Mammalian Pineal Gland is an extremely clear summary of
the state of the field and simply hums with Arendtā€™s own enthusiasm for what
has yet be disovered. For example, we donā€™t even now how melatonin entrains
the endocrine system in mammals and have only a limited understanding of its
sites of action in the brain, although the recent cloning of melatonin
receptors by Steve Reppert of Harvard University is a major advance in the
field. The book will appeal to specialists, as well as to a broader readership
of biologists and doctors. Early chapters deal with the physiology and
biochemistry of the pineal gland, the centre of the book with daily and
seasonal rhythms and the last part with therapeutic potential and sites of
action of the hormone. Perhaps if we are lucky, all of those people making
money out of melatonin by writing ill-informed articles or prescribing it for
their patients will go and buy a copy of this book. Lerner, now long since
retired from Yale, has written a brief foreword. I can do no more than repeat
his first sentence: ā€œA wonderful book ā€“ comprehensive, up to date and
beautifully writtenā€.

When Charles Darwin first proposed the concept of sexual selection,
he drew a clear distinction between natural and sexual selection: ā€˜Sexual
Selection depends on the success of certain individuals over others of
the same sex in relation to the propagation of species; while Natural Selection
depends on the success of both sexes, at all ages, in relation to the general
conditions of life.ā€™ Darwin, however, remained baffled as to how desirable
characteristics were transmitted from one generation to the next.

We now appreciate that all aspects of sexual differences ā€“ from the
gametes to the gonads, accessory glands, organs of display, differences
in body size and life expectancy, brain structure and behaviour ā€“ are likely
to be subject to sexual selection. Rather than locate all the male genes
on a male-specific chromosome, nature has adopted the ingenious solution
in mammals of locating genes that code for a testis on a single Y chromosome.

The hormones produced then interact with an array of autosomal genes
(those not involved in sexual differences) to bring about the spectacular
array of sexually dimorphic differences. Removal of these male sex hormones
by castration often results in a female body form. For instance, castrated
deer lack antlers and do not grow to the final size of males.

The isolation of the sex-determining gene in mammals was the subject
of an exciting race resulting in success for Peter Goodfellow, Robin Lovell-Badge
and colleagues in 1990. However, the mammalian system of sex determination
does not represent the only solution to the problem.

In birds, for instance, dimorphic sex chromosomes are found in the female.
Here, ovarian hormones stimulate the formation of dull plumage and actively
suppress many male characteristics. So removing the ovaries of a peahen
will induce the spectacular plumage of the male, while castrating the male
has no effect.

Interestingly, birds reveal the dual role of sex steroids on behaviour
and body form because androgens, hormones found only in males, are definitely
required for the expression of male courtship and territorial behaviour.
A chapter by John Wingfield on the ā€˜challenge hypothesisā€™ provides a lively
review of this topic in birds. A castrated peacock may have a lovely tail
but it will probably not display it, or behave as a male. It needs androgens
to do that.

The story becomes more complicated with the lower vertebrates. Some
creatures, such as snakes, have sex chromosomes while others, such as turtles
and crocodilians, rely on temperature-sensitive genes located on autosomes.
Exposure to a high or low temperature at a critical stage of development
results in a switch of a neutral body plan to a male or female phenotype.
As a result, the sex ratio in the wild is often skewed. A few vertebrates
have adopted the strategy of changing sex (fish, for example) or hermaphroditic
reproduction (common in invertebrates but generally confined to fishes in
the vertebrates). In The Differences Between the Sexes these topics are
covered, both from the point of view of mechanisms and evolutionary cost-benefit
analysis.

It is clear that sex has a cost. Males are wasteful because they cannot
bear young and represent half of the population in many species. Also, when
sperm and egg meet, there is a ā€˜cost of meiosisā€™ due to the increased probability
of losing advantageous gene combinations. So, why have so few species of
vertebrates abandoned sex for parthenogensis, in which the unfertilised
ovum develops directly into a new individual. David Crews considers this
in a masterly review of the evolution and behaviour of parthenogenetic whiptail
lizards.

This book is concerned with the differences between the sexes in the
broadest sense. It combines 22 up-to-date reviews, each written by a different
author, on the molecular mechanisms involved in sex determination, together
with genetic, hormonal, and anatomical and behavioural data from a wide
range of species, including insects, lower vertebrates, birds, mammals and
humans. It is the first book in this field to span the full breadth of modern
biology from studies of reproductive success in wild animals to lively
reviews of sex-determining mechanisms and the evolution of the sex chromosomes.

Roger Short has influenced a whole generation of reproductive and evolutionary
biologists with his writings on reproduction in mammals. Here, he and Evan
Balaban are to be congratulated for producing a beautiful collection of
reviews and essays on one of the central problems of modern biology: the
causes and evolution of the differences between the sexes. At Ā£55
it represents excellent value for money for researchers and students alike.

If you canā€™t afford a copy, borrow one and read Shortā€™s introductory
article on the role of dimorphism in gametes and why virtually all mitochondria
are maternal in origin ā€“ a feature exploited by molecular geneticists. It
should have the effect of making you give up beer for a week or so to buy
a copy.

Andrew Loudon is head of the Reproductive Biology Group at the Institute
of Zoology, Zoological Society of London.