Hormones in Mammalian Evolution
James Michael Howard
Fayetteville, Arkansas, U.S.A.
Animals that produced increased levels of prolactin and
dehydroepiandrosterone (DHEA) survived the period of mass extinctions at the
end of the Cretaceous period. DHEA increases thermogenesis and supported
existence through the extended episode of cold and dark. Further increases
in DHEA and prolactin produced continual physiological and anatomical
changes which eventually produced all of the characteristics of mammals.
Keywords: dehydroepiandrosterone, mammal, marsupial, melatonin, monotreme,
This is a new explanation of mammalian evolution. The principal hypothesis
is that increases in the hormone, prolactin, and another hormone,
dehydroepiandrosterone, which prolactin stimulates, are the basis of
survival of animals at the end of the Cretaceous period.
(Dehydroepiandrosterone increases thermogenesis, which is increased body
heat. Increased thermogenesis may be the beginning of true endothermy.)
These changes first occurred in the predecessors of mammals. Subsequent
changes in production of these hormones produced differential development in
animals which are currently identifiable as monotremes, marsupials, and
The separation and development of mammals began with selective survival of
animals that could maintain heat production during a time of prolonged cold
and darkness. (These are possible climatic consequences of a massive
meteoric impact or a time of massive volcanic activity.) The hormone,
dehydroepiandrosterone (DHEA), is an advantage during cold. Animals that
produce increased amounts of DHEA are able to produce more heat from a
limited food supply. DHEA treatment in rats affected body weight, body
composition and utilization of dietary energy by both impairing fat
synthesis and promoting fat-free tissue deposition and resting heat
production. (Tagliaferro et al. 1986). This effect of DHEA is due to
increased thermogenesis (Bobyleva et al. 1993). As cold and darkness
decreased available nutrition, individuals that could derive more benefit
from reduced nutrition had a survival advantage.
Increased DHEA was a consequence of simultaneous changes in production of
two other hormones, the production of which was affected by increased cold
and darkness. This combined change in these two hormones directly affected
DHEA production. Increased cold and reduced sunlight selected for animals
that differed in production of melatonin and prolactin. These changes in
melatonin and prolactin increased DHEA production in very early mammals.
The pineal hormone, melatonin, is released during nighttime; bright light
(sunlight) reduces production of melatonin (Kostoglou-Athanassiou et al
1998a). Therefore, reduction of sunlight, especially ultraviolet light, as
a consequence of atmospheric dust clouds, prolongs overall production of
melatonin. In some animals melatonin treatment reduces prolactin production
(Poulton et al 1986). In others, shorter exposure to melatonin stimulates a
more rapid response in prolactin production (Kostoglou-Athanassious 1998b).
This rebound of prolactin production was fundamental to survival of very
Birds and turtles exhibit a distribution of melatonin receptors that is
drastically different from that observed in mammals, where binding
predominates in the pars tuberalis of the adenohypophysis and in the
suprachiasmatic nucleus (Cassone et al. 1995). Melatonin binding sites are
much more extensive in the brains of birds and turtles. The pars tuberalis
is mainly composed of pars tuberalis-specific cells containing dense
melatonin receptors that change according to photoperiod (Wittkowski et al.
1999). The pars tuberalis is directly involved in photoperiodically
regulated changes in prolactin secretion, (Morgan 2000) because of
photoperiodic effects of melatonin on prolactin secretion, (Morgan and
I suggest the significance of a rebound of prolactin in response to
melatonin is that the rebound of prolactin is a method of avoiding lethal
suppression of brainstem activity during sleep. Melatonin secretion
increases as light diminishes (dusk). This reduces brain activity; sleep
begins. If this effect of melatonin is too deep, the brainstem also ceases
function. In order to avoid this, the prolactin rebound evolved, probably
in very early mammals as a result of changes in the pars tuberalis. The
pars tuberalis responds to melatonin suppression of nervous activity by
producing prolactin. For example, melatonin production is increased in
winter, because of reduced light. Increased melatonin in winter occurs in
bullfrog tadpoles (Wright et al. 1999) and men and women (Tarquini et al.
1997). Therefore, increased melatonin, during the winter photoperiod, could
cause torpor (dormancy, inactivity, extended sleep-like state) in
susceptible animals. Treatment induced hyperprolactinemia opposes the
actions of winter torpor in Siberian hamsters (Rudy et al. 1993). Prolactin
produces the opposite effect of melatonin. During the time of prolonged
cold and darkness, animals that did not produce increased prolactin in
response to increased and prolonged melatonin were at risk of decreased
activity (torpor) and death. The distinctive location of melatonin
receptors in the pars tuberalis and suprachiasmatic nucleus of mammals,
along with reduced melatonin receptors elsewhere in the brain could have
been an advantage to very early mammal-like organisms. The response that
results from the prolactin rebound would have a greater effect in a brain
that does not have widespread melatonin receptors, as is found in birds and
reptiles. That is, the mammalian brain is deactivated less by nighttime
melatonin, and, therefore, is more easily aroused from sleep. (A variation
on the activity of the melatonin induced prolactin rebound may be involved
in evolution of nocturnal animals. A failure in the melatonin induced
prolactin rebound, in humans, may be an explanation of sudden infant death
The advantage of increased prolactin is that prolactin directly stimulates
DHEA production. The usual neurohormone given credit for stimulating DHEA
production is adrenocorticotropic hormone (ACTH). However, it may be shown
that not only is prolactin more effective in stimulating DHEA, but prolactin
may be specific for stimulating DHEA (Albrecht and Pepe 1987; Pepe and
Albrecht 1985). Organisms that produce increased DHEA have an advantage
during prolonged cold and darkness; they are warmer.
The close coupling of increased prolactin and DHEA started formation of the
cluster of physiological and anatomical characteristics that define mammals.
Breasts are modified apocrine glands. Apocrine glands exhibit receptors for
prolactin in mice (Choy et al. 1995) and the sulfate of DHEA, DHEAS, is
found in human apocrine glands (Labows et al. 1979). The increase of
prolactin and DHEA in very early mammals may have participated in the
formation of hair and apocrine glands that provided calorie enriched
products for underdeveloped offspring. This level of development occurs in
monotremes, organisms which lay eggs but provide nutrition to young secreted
onto hair of the abdomen. Fully functional breasts would provide
significant selection value. DHEA is significantly correlated with each
stage of human breast development before and after the onset of menarche.
(Murakami et al. 1988).
I suggest the expansion of nervous tissues in invertebrates and the
enlarged brains of vertebrates may have evolved because of increased use of
DHEA by nervous tissues. DHEA and DHEAS are neuroactive and both are
imported into the brain from the circulation and produced in the nervous
system. (Baulieu 1999). The brain manufactures its own DHEA and takes DHEA
from the blood. The increase in DHEA that may have produced the very early
mammals may have increased subsequent brain size and development. I think
the brains use of DHEA is exaggerated compared to other tissues. (It is
also my hypothesis that reduced facial prognathism, dentition size, and
postcranial skeleton (neotony) of Homo spaiens, compared to pre-existing
hominids, results from use of DHEA by the larger brain of H. sapiens.
Chimpanzees have smaller brains, more facial prognathism and larger teeth,
as a result of increased DHEA. Chimpanzees extra DHEA is available for
increased growth of all of these structures.) The foregoing was intended to
demonstrate that it is possible that use of DHEA for heat production and
brain development in early mammals may have reduced available DHEA used for
egg shell production. That is, one tissue, or function, competes for DHEA
with all others. The increasing brain of very early mammals may have
reduced egg shell formation. Therefore, extraembryonic tissues within the
egg, already doing the jobs of a placenta, and already formed, may have
developed into placentas simply as a consequence of lack of an egg case.
That is, evolution of the placenta from these egg structures required little
evolutionary change, and less energy expenditure, than that necessary for
evolution of an entirely new system of internal development of offspring.
It is noteworthy that the Platypus, a monotreme, has a brain that is not
highly developed and lays eggs; the brain is not excessive in taking DHEA at
the expense of egg shell formation. Marsupials, with more developed brains,
are examples of a later stage of mammals which produce live births. After a
short gestation, marsupials produce a small, underdeveloped neonate. This
represents an example of gestation without an egg shell. The change from
oviparity to viviparity coincides with development of a placenta and a
larger brain. Animals that could produce more DHEA exhibited increased
survival, increases in brain size, and increased viviparity. Further
increases in DHEA and prolactin would increase the development and
functionality of the placenta and breasts, coincidentally.
Increased prolactin and dehydroepiandrosterone may have increased survival
of animals during the late Cretaceous period. This survival advantage is
due to increased and continuous body temperature. This is the rise of
endothermic animals and animals that could synchronize reproduction with the
most propitious time for growth and development of offspring. That is, as
melatonin production decreases as sunlight increase, DHEA production would
increase during times of overall warmth. Therefore, the extra DHEA could be
used more for growth and development, rather than for heat production as the
earth increased in warmth and sunlight.
endothermy continued to be a strong advantage during the cold periods of
the Cenozoic. Transitional animals, the monotremes and marsupials, exist
and support a pattern of increases in prolactin and DHEA. DHEA is directly
involved in growth, development, and function of all mammalian
characteristics, especially the brain. Increased dehydroepiandrosterone may
be the basis of evolution of mammalia.
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