Hormones in Mammalian Evolution

Copyright 2001, James Michael Howard and Rivista di Biologia / Biology Forum 2001; 94: 177-184

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.

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 advanced mammals.

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 early mammals.

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 Williams 1996).

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 syndrome.)

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 brain's 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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James Michael Howard

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