News Physiol Sci 14: 223-231, 1999;
1548-9213/99 $5.00
News in Physiological Sciences, Vol. 14, No. 6, 223-231,
December 1999
© 1999 Int. Union Physiol. Sci./Am. Physiol. Soc.
Prolactin, the Hormone of Paternity
Carsten Schradin and
Gustl Anzenberger
C. Schradin and G. Anzenberger are in the Anthropologisches Institut und Museum, Universität Zürich-Irchel, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
 |
Abstract
|
|---|
Prolactin has long been known to play a significant role in maternal care. When behavioral endocrinologists began to examine the endocrinology of fatherhood, prolactin was also found to be connected with paternal care in fish, birds, and mammals including primates.
|
Introduction
|
|---|
More than 200 effects in growth, reproduction, osmoregulation, and immunology have been documented for prolactin (PRL). Although PRL seems to be an omnipotent hormone ("omnipotin"), it is best known for its role in the production of milk proteins. However, PRL is not only essential for the physiology of lactation in female mammals; it also plays a significant role in maternal care. Nulliparous female rats that have been primed with steroids (estradiol and progesterone) and exposed to foster pups for 2 days show maternal care and an increase in plasma PRL level (13). Nulliparous, hypophysectomized female rats treated with progesterone and estradiol do not show maternal care, but they do so when they are simultaneously treated with ovine PRL. Thus, although PRL is essential for the onset of maternal care in rats, priming with steroids is necessary to induce this effect. Because PRL prepares the physiology of the female for lactation and maternal behavior, PRL is often referred to as "the hormone of maternity." However, PRL has also been recognized to play a significant role in paternal behavior, and we deal with this aspect in the next sections.
|
PRL in "paternal" male rats
|
|---|
When scientists began to examine the endocrinology of paternal care, they used one of their favorite laboratory subjects, the male rat. Although male rats normally do not participate in caregiving behavior for the young, it is possible to induce maternal-like behavior in male rats by exposing them to foster pups. However, males show longer latencies of parental response than virgin females, they do not always show full paternal care, and some do not respond paternally at all (13). Indeed, infanticide is often shown by male but not by female rats exposed to pups (3).
Male rats exhibiting paternal behavior do not show an increase in serum PRL level, even when primed with steroids (13). This result led to the proposal that steroid-primed female and male rats generally respond similarly in the behavioral response toward foster pups but not in the endocrine response. A possible reason for this difference was supposed to reside in the absence of nipples in male rats, because tactile stimulation of the nipples may be essential for release of PRL. Accordingly, male rats were exposed prenatally to flutamide (an antiandrogen) so that they developed nipples. But even after castration and priming with estradiol and progesterone, respectively, these "males" did not show a change in PRL concentration when exposed to foster pups (14).
|
Animal fathers that naturally show paternal behavior
|
|---|
Quite different results are obtained when the endocrinology of fatherhood is studied in species in which the fathers naturally display caregiving behavior toward their young. Such studies have been conducted on several species ranging from fish to primates. Most of these species are socially monogamous, and both mother and father show parental care. In a few vertebrate species, however, exclusive paternal care occurs (in some fish, amphibians, and birds), which means that the father is the only caretaker. Paternal care can be direct or indirect. Direct paternal care includes all actions of fathers toward their young that exert an immediate physical influence on them and are thought to increase their survival rate (e.g., feeding, warming, and playing). Indirect paternal care includes acts of the father that are advantageous for the young but are shown by the male independently of the presence of the young (e.g., defense of a territory maintaining critical resources; Ref. 9). The following discussion is restricted to direct paternal care.
|
Prolactin in fish fathers
|
|---|
In two fish species with exclusive paternal care, a causal relationship between PRL and paternal care has been found. In the North American bluegill (Lepomis macrochirus), males construct nests in colonies (8). Females visit the nests to spawn and then disappear, leaving males alone with the offspring. Paternal care shown by male bluegills includes fanning the eggs (to deliver O2) and protecting the eggs and larvae from predators until the fry leave the nest. Male bluegills were caught in the field after spawning had occurred. Some males were implanted with bromocriptine pellets, others with placebo pellets, and a third group was only handled. Each fish was released back into its territory <2 min after it had been captured. Bromocriptine is a dopamine-receptor antagonist that inhibits endogenous PRL secretion. As a protein, PRL has a species-specific amino acid sequence. Nevertheless, PRL of phylogenetically closely related species can usually be measured with the same immunoassay [radioimmunoassay (RIA), immunoradiometric assay (IRMA), or enzyme immunoassay (EIA)]. Special assays for some bird and mammal species exist, but there is no assay for fish PRL, other than bioassays testing for special physiological effects known to be PRL dependent (see below). For this reason, the actual serum level of PRL in fish is unknown. However, by reducing endogenous PRL secretion with bromocriptine, the problem of the unknown natural PRL level in bluegills was elegantly resolved.
Bromocriptine-treated males showed less total aggression toward a predator model in comparison with both control groups. By contrast, they showed more ring circling, a behavior pattern typical for nesting males (indicating that there are no eggs in their nests). This reduced the time available for fanning eggs, and >75% of the eggs of bromocriptine-treated males were infected with fungus, whereas <25% of the eggs of control males were infected. Thus the inhibition of endogenous PRL secretion not only significantly reduced paternal care, it also reduced the reproductive success of these males (8).
Corresponding results were found with another exclusively paternal fish, the three-spined stickleback (Gasterosteus aculeatus). Like bluegills, male sticklebacks construct nests in which the females spawn. When male sticklebacks are nesting but not yet brooding, they show a constant low fanning rate. When males were implanted with pituitaries from nonbreeding donor stickleback males, the fanning rate increased. However, the fanning rate of treated males was not as high as that of breeding males, indicating that PRL is not the only factor necessary for the occurrence of paternal care in sticklebacks. An increase in the PRL level was confirmed using a bioassay. The number of mucocytes in the epithelium of the skin increased, and this is known to be PRL dependent. In brooding sticklebacks, on the other hand, no increase in the fanning rate was observed after they received pituitary implants. Because brooding males show a very high fanning rate, it is likely that this behavior pattern was already at its maximal level and could not be increased by additional PRL (5).
In early studies, a fascinating relationship between PRL and parental care was found in the monogamous blue discus (Symphysodon aequifasciata), a popular aquarium fish (Fig. 1A
). Male and female discus fish show the same pattern of paternal care, and they also show the same response to experimentally enhanced PRL titers. Injection of PRL not only leads to an increase of fanning behavior (Fig. 2), it also leads to an increase of mucus cell production. These epidermal cells produce mucus as food for the fry. By analogy with the milk of mammals, this mucus is called "discus milk" (1).
View larger version (100K):
[in this window]
[in a new window]
|
FIGURE 1. Representatives from 3 different classes of vertebrates for all of which a correlation between prolactin (PRL) and parental behavior could be shown. A: discus fish surrounded by fry that have been nourished by PRL-dependent discus milk (photograph by G. Weissflog). B: pair of ring doves with a squab that has been provisioned during the first days after hatching exclusively by PRL-dependent crop milk (photograph by G. Gronefeld). C: common marmoset carrying a twin set of offspring. In this species, the male provides almost all infant care apart from lactation (photograph by G. Anzenberger).
|
|
View larger version (9K):
[in this window]
[in a new window]
|
FIGURE 2. Causal relationship between PRL and paternal care. Open bars, controls; filled bars, individuals that received PRL. Left: peripherally injected PRL induces fanning behavior in discus fish (after Ref. 3). Middle: significantly more ring doves show parental feeding after peripheral PRL injections than individuals that received vehicle (after Ref. 4). Right: more ring doves show parental feeding after intracerebroventricular injections of PRL than of vehicle. Subjects were food deprived to minimize confounding effects of crop sacs filled with seed (after Ref. 4).
|
|
|
Prolactin in bird fathers
|
|---|
Most bird species are socially monogamous, with both mothers and fathers showing paternal care. Paternal care in birds can be divided into two phases: 1) prehatching phase (incubation) and 2) posthatching phase (brooding and feeding the young). Table 1 summarizes studies that have examined the relationship between PRL and parental care in different bird species (4). Although most studies showed only a correlative relationship, with enhanced PRL levels during one or both phases of paternal care, the large number of such studies is in itself impressive. In 25 species of 9 orders ranging from penguins to songbirds, some relationship between PRL and paternal care was found (4). In male birds, PRL typically increases during incubation, either being elevated during brooding or gradually decreasing after hatching (example in Fig. 3). This suggests that PRL is an important factor for paternal care in birds. The fact that the same endocrine pattern is found in maternally behaving female birds provides further evidence for the important role of PRL in caregiving behavior in birds. Another strong indication comes from two studies of species with helpers at the nest. Helpers are nonbreeding individuals that take part in rearing the young. In Harris' hawks and Florida scrub jays, these helpers also show elevated PRL levels (4). Yet more evidence comes from studies of two bird species with exclusive paternal care. In Wilson's and red-necked phalaropes, males perform all incubation and brood care and also show an increase in PRL level during this period, whereas females do not (4).
View larger version (10K):
[in this window]
[in a new window]
|
FIGURE 3. Correlation between PRL and fatherhood. Open bars, nonfathers; filled bars, fathers. Values for California mouse were divided by 10 and values for marmoset multiplied by 10 to fit them to within range of the other species. (King penguin, after Cherel et al., 1994., cited in Ref. 4; California mouse, after Gubernick and Nelson, 1989, cited in Ref. 6; wolf, after Ref. 7; marmoset, after Dixson and George, 1982, cited in Ref. 15.)
|
|
A causal connection between PRL and parental care has been demonstrated in the ring dove (Fig. 1B
). Both male and female ring doves that received injections of PRL for 7 days showed more parental care toward foster young than controls that received only vehicle injections (Ref. 4; Fig. 2). In ring doves, it is not only the occurrence of paternal care that is PRL dependent but also the production of crop milk, a curdlike substance produced in the crop sac and used to feed the young (4). Once again, this is an analogy not only to mammalian milk (and discus milk) but also to endocrine regulation of endogenously produced food for young.
Although a connection between PRL and parental care exists in birds, this relationship is not simple. For example, sex differences in incubation (sitting time on eggs) do not always correlate with sex-biased differences in PRL level (Table 1). In facultatively polygynous birds (e.g., starlings), males do not usually incubate when paired with several females but do when they are mated monogamously. Nevertheless, polygynous males do have elevated PRL levels similar to those of monogamous males (4). A relationship between PRL titer and incubation motivation may nevertheless exist in polygynous males. If they have to divide up their time between several females (e.g., mate guarding to avoid extrapair copulation of their females), they may have no time available for incubation. No simple explanation can be given for elevated PRL levels in breeding cowbirds, a brood parasite that shows no parental care. One explanation could reside in the circannual cycle of PRL excretion, with increased PRL levels stimulated by increasing day length correlating with the breeding season, which has been observed in several bird species (4). However, this does not answer the question concerning the physiological function of enhanced PRL levels in cowbirds.
|
Prolactin in mammalian fathers
|
|---|
Only 3-5% of mammalian species are socially monogamous, and not all monogamous mammals exhibit paternal care. For this reason, there have been only a few studies of the endocrinology of paternal care in mammals. Those that have been conducted confirm the pattern found in the other vertebrate classes.
In the California mouse (Peromyscus californicus), males show the same amount of paternal care as females, with the obvious exception of lactation. Fathers build nests, carry young, lick them, and spend a large amount of their time in the nest in physical contact with them (warming the pups). Fathers have significantly higher plasma PRL titers than nonfathers (Fig. 3). Under experimental conditions, fathers show more caregiving behavior toward strange pups than nonfathers (which often commit infanticide). The PRL levels of fathers are similar to those of mothers (6).
Some carnivores, such as wolves, show a communal breeding system. In wolves, it is not only the mother (alpha female) that nurses the young but also other females, which experience pseudopregnancy with elevated PRL levels. Even males, including the father (alpha male), participate in caregiving: regurgitation of food, licking pups, playing with pups, and defending them. Parturition followed by parental care occurs in spring, coinciding with a seasonal PRL peak in both sexes. In wolves, therefore, both fathers and helpers have enhanced PRL levels during the period of infant care (Ref. 7; Fig. 3).
Among primates, one group of New World monkeys—-the Callitrichidae—-is well known for extensive paternal care. Callitrichids (marmosets and tamarins) live in family groups with one breeding pair and offspring of successive births, all of which help rear the young. The father carries the offspring on his back (Callitrichidae generally have twins) and shares food with them (Fig. 1C). The endocrinology of fatherhood has been studied in two species of callitrichids. In common marmosets (Callithrix jacchus), fathers have significantly higher plasma PRL levels than nonfathers (Fig. 3). In a noninvasive study, PRL was measured in urine samples collected with a stress-free method from cotton-top tamarins (Saguinus oedipus). Not only did fathers have significantly higher PRL levels than nonfathers, but PRL levels already began to increase 2 wk before birth and reached a maximum in the 2 wk after birth. This indicates that enhancement of the PRL level in cotton-top tamarin fathers is not simply caused by stimuli from the infants (15). If PRL induces paternal care in tamarins, the enhancement of PRL would be expected to occur before birth, because the fathers begin to carry their infants immediately after birth.
A very high degree of paternal care occurs in one other primate species, but to date no endocrine studies have been performed. There is an ongoing discussion about the extent to which paternal care is a cultural or a biological characteristic of Homo sapiens (11). In an interview study, a high emotional attachment of fathers to their newborn was found, referred to as engrossment (11). However, some fathers reported that they themselves were quite surprised about the strong emotions they felt for their child. This indicates that their answers were not only based on cultural expectation ("human fathers have to love their children") but showed that they really loved their newborn. A physiological process is likely to underlie this emotional bond, independently of the way it depends on cultural factors. Hormones, especially PRL, may be one physiological factor, and studies of the endocrinology of fatherhood in humans are needed. That PRL may play a role in the human male is suggested by a study in which stimulation of the breast and nipples by the partner resulted in an increase in serum PRL in both women and men (10).
|
Neural actions of prolactin during fatherhood
|
|---|
Hormones can directly modulate behavior when they act in the central nervous system (CNS). Ring doves receiving PRL intracranially show significantly more parental behavior toward foster chicks than do vehicle-treated doves (Ref. 4; Fig. 2). Two modes of action of hormones in the CNS are conceivable: 1) organizational effects changing the neural substrate and 2) activating effects changing neural action. Organizational effects could provide an explanation for the continuation of paternal care even after the PRL level begins to decrease (some birds, callitrichids), although this hypothesis has not yet been tested. In cotton-top tamarins, a decrease in PRL level already occurs 2 wk after birth (11), although males continue to carry infants for several weeks (infants first becoming totally independent of carriers at an age of ~12 wk). In fact, PRL seems to be important for the onset rather than for the maintenance of paternal care.
Because PRL is a protein with ~200 amino acids, the question arises as to whether and by what means PRL can pass from the blood into the brain despite the blood-brain barrier. In fact, several studies showed that PRL is able to pass from the blood into the brain. The choroid plexus, which shows specific binding sites for PRL, is thought to play a major role in this process (4).
In the exclusively paternal fish Lepomis gibbosus, a population of neurons in the area dorsalis of the telencephalon is known to be activated by PRL, and combined injections of testosterone and PRL induce fanning behavior in this species. This finding is only correlative and does not show a direct connection between these neurons and parental care, but the corresponding neurons in two other fish species (Carassius auratus and Idus idus) that show no parental care are far less sensitive to PRL than in L. gibbosus (2).
In birds, the preoptic area (POA) shows specific binding for PRL and has hence been suggested to play an important role in PRL-induced parental care. Interestingly, the POA is less PRL sensitive in cowbirds, brood parasites showing no parental care, than in starlings, which show parental care. Ring doves with lesions of the POA do not exhibit PRL-induced parental care. A significant negative correlation exists between the extent of POA damage and the amount of parental behavior. In other words, the greater the lesioning of the POA, the less parental behavior is shown. In Wilson's phalarope, a bird species with exclusive paternal care, incubating males show a higher PRL sensitivity in the POA compared to females and to nonincubating males (4).
In female rodents, the medial preoptic area (MPOA) is known to be important in the control of maternal care. In the biparental California mouse, virgin males have a larger MPOA than virgin females, although virgin mice of both sexes show no parental care. However, this sex difference in the volume of the MPOA is no longer found in parentally behaving California mice because of increase in soma size of the MPOA of females. PRL is known to facilitate maternal care in female rats when implanted into the MPOA, but nothing is known about PRL sensitivity of the MPOA in the California mouse or its role in parental care (6).
|
Conclusions
|
|---|
PRL is an important factor in the occurrence of paternal care and thus deserves the label "hormone of paternity." In combination with its role in maternal care, it might in fact more properly be called the "hormone of parenthood." PRL is clearly not an exclusively female hormone but also has important actions in male vertebrates. A connection between PRL and paternal care has been shown in numerous species in three classes of vertebrates: fish, birds, and mammals. Hence, the correlation between PRL and paternal (and maternal) care seems to be a general feature of vertebrates.
Unfortunately, nearly all studies have been correlative (Fig. 3). Only in fish and ring doves are the data sufficient to suggest a causal relationship (Fig. 2). Clearly, more research should be conducted into the causality of the relationship between PRL and paternal care. In frogs, many species show paternal care, ranging from egg guarding through tadpole transport to breeding of tadpoles in the inguinal pouch (12), but it is not known whether PRL plays a role in these processes. In mammalian carnivores, where many species show paternal care, studies are also needed. The results for wolves cited above show only a correlation between seasonal enhancement of PRL levels and parental care (7). As many social carnivores have been studied intensively, it is surprising that nothing is known about the endocrinology of caregiving behavior in these species.
Although the indications of a relationship between PRL and paternal care are overwhelming, it is clear that PRL cannot be the only factor. Like any other life-sustaining physiological process, caregiving behavior is a very important factor, because it contributes directly to the representation of the father's genes in the next generation. It is extremely unlikely that paternal care would depend on a single factor only, as this would render it highly susceptible to defects. Life-sustaining processes generally depend on numerous factors as a kind of insurance, so that they will continue to operate, albeit at a reduced level, after the breakdown of one factor. Male bluegills with inhibited endogenous PRL secretion after bromocriptine treatment show reduced paternal care in comparison to controls, but they nevertheless show some paternal care and have a degree of reproductive success (8). Female rats exposed to foster pups for 5 days show maternal care despite the fact that they exhibit no increase in serum PRL level (13).
In female rats, priming with estradiol and progesterone reduces the latency until maternal care is shown from 5 to 2 days and there is an accompanying increase in serum PRL level (13). This reveals another important point: cooperation between different factors. Steroid hormones (estradiol and progesterone) are important for the action of PRL in birds. They are thought to have a priming function, possibly enhancing PRL secretion and/or enhancing sensitivity of the neural system to PRL. One possible explanation for this phenomenon may be an increase of PRL-receptor production induced by steroids (4). Other possible factors influencing the occurrence of paternal care in addition to PRL are neonatal hormone levels, changes in steroid hormone concentrations, experience of the male (social and sexual experience, previous rearing of young), and stimuli emanating from pups (3).
The main aim of further studies should be proper demonstration of the causal connection between enhanced PRL levels and parental care and, in an integrative approach, determination of connections between the different factors responsible for parental care.
|
Acknowledgments
|
|---|
The authors are grateful to Dr. S. P. Mendoza and Dr. R. D. Martin, who both provided constructive comments that significantly improved the manuscript. The manuscript was written during the first author's work as doctoral student supported by a Swiss National Science Foundation grant (31-49 656.96 to G. Anzenberger).
|
References
|
|---|
-
Blüm, V., and K. Fiedler. Hormonal control of reproductive behavior in some cichlid fish. Gen. Comp. Endocrinol. 5: 186–196, 1965.
-
Blüm, V., and K. Fiedler. Prolaktinempfindliche Strukturen im Fischgehirn. Fortschr. Zool. 25: 155–166, 1974.
-
Brown, R. E. Hormonal and experiential factors influencing parental behaviour in male rodents: an integrative approach. Behav. Proc. 30: 1–28, 1993.
-
Buntin, J. D. Neural and hormonal control of parental behavior in birds. Adv. Stud. Behav. 25: 161–213, 1996.
-
De Ruiter, A. J. H., S. E. Wendelaar Bonga, H. Slijkhuis, and B. Baggerman. The effect of prolactin on fanning behavior in the male three-spined stickleback, Gasterosteus aculeatus L. Gen. Comp. Endocrinol. 64: 273–283, 1986.[Medline]
-
Gubernick, D. J., D. R. Sengelaub, and E. M. Kurz. A neuroanatomical correlate of paternal and maternal behavior in the biparental California mouse (Peromyscus californicus). Behav. Neurosci. 107: 194–201, 1993.[Medline]
-
Jöchle, W. Prolactin in canine and feline reproduction. Reprod. Domest. Anim. 32: 183–193, 1997.
-
Kindler, P. M., J. M. Bahr, M. R. Gross, and D. P. Philipp. Hormonal regulation of parental care behavior in nesting male bluegills: do the effects of bromocriptine suggest a role for prolactin? Physiol. Zool. 64: 310–322, 1991.
-
Kleiman, D. G., and J. R. Malcolm. The evolution of male parental investment in mammals. In: Parental Care in Mammals, edited by D. J. Gubernick and P. H. Klopfer. New York: Plenum, 1981, p. 347–387.
-
Kolodny, R. C., L. S. Jacobs, and W. H. Daughaday. Mammary stimulation causes prolactin secretion in non-lactating women. Nature 238: 284–285, 1972.[Medline]
-
Lamb, M. E., J. H. Pleck, E. L. Charnov, and J. A. Levine. Paternal behavior in humans. Amer. Zool. 25: 883–894, 1985.
-
McDiarmid, R. W. Evolution of parental care in frogs. In: The Development of Behavior, edited by G. M. Burghardt, and M. Behoff. New York: Garland STPM, 1978, p. 127–147.
-
Samuels, M. H., and R. S. Bridges. Plasma prolactin concentrations in parental male and female rats: effects of exposure to rat young. Endocrinology 113: 1647–1654, 1983.[Abstract/Free Full Text]
-
Tate-Ostroff, B. A., and R. S. Bridges. Nipple development and pup-induced prolactin release in male rats treated prenatally with the antiandrogen flutamide. Psychoneuroendocrinology 13: 309–319, 1988.[Medline]
-
Ziegler, T. E., F. H. Wegner, and C. T. Snowdon. Hormonal responses to parental and nonparental conditions in male cotton-top tamarins, Saguinus oedipus, a New World monkey. Horm. Behav. 30: 287–297, 1996.[Medline]
This article has been cited by other articles:
|
|
|
|
 
C. Schradin
Differences in prolactin levels between three alternative male reproductive tactics in striped mice (Rhabdomys pumilio)
Proc R Soc B,
May 7, 2008;
275(1638):
1047 - 1052.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Gregg, V. Shikar, P. Larsen, G. Mak, A. Chojnacki, V. W. Yong, and S. Weiss
White Matter Plasticity and Enhanced Remyelination in the Maternal CNS
J. Neurosci.,
February 21, 2007;
27(8):
1812 - 1823.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. Freeman, B. Kanyicska, A. Lerant, and G. Nagy
Prolactin: Structure, Function, and Regulation of Secretion
Physiol Rev,
October 1, 2000;
80(4):
1523 - 1631.
[Abstract]
[Full Text]
[PDF]
|
|
|
Top
Introduction
PRL in "paternal" male...
