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D Crews

Publications and source records attributed to D Crews.

At least 55 records · Page 3Linked to original sources

Effect of long-term castration and long-term androgen treatment on sexually dimorphic estrogen-inducible progesterone receptor mRNA levels in the ventromedial hypothalamus of whiptail lizards.

In whiptail lizards, as in laboratory rodents, females will respond to exogenous estrogen by increasing progesterone receptor (PR) or PR mRNA in the ventromedial hypothalamus (VMH) while males show an attenuated response to the same treatment. In rodents, neonatal hormone manipulations affect the adult expression of this trait; however, few investigators have examined the effects of hormone treatment in adulthood. Therefore the current study was carried out to determine whether observed sex differences in the estrogen response in adulthood may be modified by steroid hormone manipulation. We castrated male whiptail lizards for 1 week (short term) or 6 weeks (long term). We also gonadectomized female whiptails and implanted them with either a Silastic capsule containing testosterone or an empty capsule. At the end of that time all implants were removed and the animals were injected with either estradiol benzoate (EB) or steroid suspension vehicle and their brains were assayed for PR mRNA expression using in situ hybridization. The results demonstrate that in male whiptail lizards, long-term castration increases sensitivity to estradiol as measured by induction of PR mRNA in the VMH; EB-injected long-term castrated males were not different from EB-injected females. However, long-term androgenization did not attenuate the estrogen response in females. This suggests that attenuation of the estrogen response in males requires activation by testicular secretions, but that females cannot be made to show a male phenotype via testosterone administration.

Age Factors↗

Regulation of male sexual behavior by progesterone receptor, sexual experience, and androgen.

Recent studies have demonstrated that physiological doses of progesterone may facilitate the androgen-dependent display of male sexual behavior in laboratory rats and three species of lizard. We used mice with a targeted disruption of the progesterone receptor to investigate whether such interactions exist in male mice and whether they may be modified by sexual experience. We found that naive intact male progesterone receptor knockout (PRKO) mice exhibit reduced mount frequencies compared to wild-type (WT) mice. Also unlike WT mice, sexually experienced PRKO males show profound losses in many measures of sexual behavior following castration. In a second experiment, we tested whether male mice heterozygous for a null mutation at the progesterone receptor locus were responsive to testosterone and progesterone treatment. We found that heterozygous males showed a reduced response to testosterone. The data are consistent with experiments indicating that the progesterone receptor is able to facilitate male-typical sex behaviors in other species and suggest novel mechanisms underlying the interaction of androgens and experience.

Androgens↗

The evolutionary antecedents to love.

Behaviors are adaptations to the physical, biotic, and social environments. Great diversity exists among vertebrates in reproductive behaviors and the neuroendocrine mechanisms underlying these behaviors. Study of this diversity illuminates species, population, and sex differences in hormone-brain-behavior relations. It also can provide insights into how and why certain neuroendocrine mechanisms evolved. Discoveries in evolution and ecology, neuroscience and endocrinology, are complementary and interrelated, and when applied in behavioral neuroscience, the investigator's perspective is less constrained by existing dogma. Naturally-occurring organisms not typically studied can be especially useful as their unusual adaptations illustrate alternative solutions to particular problems. Indeed, they 'often force one to abandon standard methods and standard points of view' with the result that, 'in trying to comprehend their special and often unusual adaptation, one often serendipitously stumbles on new insights' (Bartholomew, 1982). Thus, to ignore comparative research would greatly limit our understanding of the evolution of hormone-behavior relations. As Bullock (1984) admonishes, "without due consideration of the neural and behavioral correlates of differences between higher taxa and between closely related families, species, sexes, and stages, we cannot expect to understand our nervous systems or ourselves".

Animals↗

Developmental effects on intersexual and intrasexual variation in growth and reproduction in a lizard with temperature-dependent sex determination.

The mechanisms that control growth and reproduction have received considerable attention by molecular and cellular endocrinologists, yet there has been relatively little effort to link these two aspects of physiology. On the other hand, evolutionary biologists have long commented on the relationship between growth and reproduction in many species, yet have generally neglected the mechanisms underlying such complex traits. An approach that integrates the multiple proximate levels promises to provide significant insight into the evolution of neuroendocrine control mechanisms. In this chapter, we take this approach in reviewing environmental influences on growth and reproduction in the leopard gecko, Eublepharis macularius. In this species, incubation temperature during embryonic development not only determines gonadal sex, but also underlies within-sex differences in growth, adult morphology, aggressiveness, reproductive physiology and behaviour, and brain organization. Thus, the leopard gecko is an excellent model to elucidate the developmental interactions among the environment and the endocrine and nervous systems that control growth and reproduction.

Animals↗

Cloning and in situ hybridization analysis of estrogen receptor in the developing gonad of the red-eared slider turtle, a species with temperature-dependent sex determination.

Many reptiles exhibit temperature-dependent sex determination where the incubation temperature of the egg determines the gonadal sex of the individual. If exogenous estrogen is administered during the temperature-sensitive period to embryos incubating at a male-producing temperature, the temperature effects can be overridden and females will be produced. Inhibiting production of endogenous estrogens at female-biased incubation temperatures results in embryos developing as males rather than females. Thus, estrogen-estrogen receptor-dependent mechanisms appear to play a key role in female sex determination. The present study characterized the expression of the estrogen receptor during the critical period of temperature sensitivity in the red-eared slider turtle, Trachemys scripta. Polymerase chain reaction was used to amplify estrogen receptor cDNA. A portion of the estrogen receptor cDNA was used to produce probes for in situ hybridization analyses to localize and quantitate levels of estrogen receptor mRNA at different stages of development in embryos from different incubation temperatures. Estrogen receptor mRNA is expressed in the gonadal tissues of both putative males and putative females even before the gonads begin to resolve as ovaries or testes. There is a greater abundance of estrogen receptor mRNA in putative females at the beginning of the temperature-sensitive period as compared to putative males. In embryos from a female-producing incubation temperature, levels of estrogen receptor mRNA are higher in the beginning of the temperature-sensitive window compared to levels after the ovary is differentiated. These results support the hypothesis that estrogen-estrogen receptor dependent processes are important during sex determination and gonadal differentiation in temperature-dependent sex determination.

Amino Acid Sequence↗

Synergistic responses of steroidal estrogens in vitro (yeast) and in vivo (turtles).

Many environmental agents exert estrogenic activity. Previous studies from our laboratories demonstrated that certain combinations of environmental estrogens (i) reverse the sex of male turtle embryos in a synergistic manner (Bergeron et al., (1994) Environ. Hlth Perspect. 102, 780-782), and (ii) synergistically transactivate the human estrogen receptor (hER) in yeast and mammalian cells (Arnold et al., (1996) Science 272, 1489-1492). Because our findings with synthetic estrogens suggested that combinations of naturally-occurring steroidal estrogens might also produce synergistic activity of the ER, we used the same model systems to measure the activity of combinations of steroidal estrogens. The activity of combinations of estrone, estradiol-17beta or estradiol-17alpha in yeast strains expressing hER was synergistic at submaximal concentrations of both estrogenic compounds. However, synergy was not observed with mixtures of estrogens when the concentration of one of the estrogens alone was maximally active in yeast. Ligand-binding assays in yeast performed with various radiolabeled estrogens suggested that multiple estrogens may interact with the receptor. The estrogen-dependent process of sex-reversal of turtle embryos incubated at a male-producing temperature was used to determine whether steroidal estrogens also had synergistic activity in vivo. In this instance, a combination of estriol and estradiol-17beta was effective in reversing the gonadal sex of turtle embryos from males to females in a synergistic manner. Our results suggest that the synergy of some combinations of estrogens, synthetic or steroidal, may play a role in the estrogen-dependent process of sexual development in certain species.

Animals↗

Effects of age and sociosexual experience on the morphology and metabolic capacity of brain nuclei in the leopard gecko (Eublepharis macularius), a lizard with temperature-dependent sex determination.

In vertebrates having sex chromosomes, sexual behavior is influenced by steroid hormones throughout life as well as by the cumulative experiences of the individual. Because males and females differ genetically as well as hormonally, it would be valuable to distinguish the contribution of sex-specific genes from hormones. In addition, since animals age as they gain sociosexual experience, but do not necessarily gain sociosexual experience as they age, it is important to separate the effects of age from those attributable to experience. The leopard gecko is a lizard lacking sex chromosomes, depending instead upon the temperature during incubation to establish gonadal sex. This effectively removes sex-specific genetic influences from any study of sexual differentiation. Eggs were incubated at either 26 degrees C or 32.5 degrees C, temperatures that produce only female hatchlings or a male-biased sex ratio, respectively. By raising geckoes in isolation and then housing some animals together in breeding groups at different ages after they attained sexual maturity, it was possible to assess the relative effects of age and sociosexual experience on the volume and metabolic capacity of limbic and non-limbic brain areas. In general, males showed more changes compared to females. For example, there was a decrease with age in the volume of the preoptic area and the ventromedial hypothalamus in males, but not in females. Both age and sociosexual experience influenced cytochrome oxidase activity in these and other brain areas. Experienced animals had greater metabolic capacity in nuclei functionally associated with sociosexual behavior in lizards and other vertebrates. For example, cytochrome oxidase activity was higher in the anterior hypothalamus of males, in the ventromedial hypothalamus of both males and females from the male-biased incubation temperature, and in the preoptic area of females from both incubation temperatures. These differences were not paralleled by differences in circulating levels of sex hormones; only plasma androgen levels differed as a function of experience in males. These data suggest that the volume and metabolic capacity of specific brain regions change as animals age and gain sociosexual experience, but the nature and degree of change depend upon prenatal events.

Age Factors↗

Independent effects of incubation temperature and gonadal sex on the volume and metabolic capacity of brain nuclei in the leopard gecko (Eublepharis macularius), a lizard with temperature-dependent sex determination.

The extent to which variation within and between the sexes can be assigned to genes vs. environment is problematic, because, in most vertebrates, males and females differ genetically. However, factors other than sex chromosomes and the consequent sex-typical gonadal hormone secretions may play important roles in the differentiation of the neural mechanisms underlying individual and sex differences in aggressive and sexual behavior. The leopard gecko, like many oviparous reptiles, lacks sex chromosomes. Instead, gonadal sex is determined by temperature during embryogenesis, with low and high incubation temperatures producing females and intermediate temperatures producing mixed sex ratios. In essence, this allows for the study of individual and sex differences without the confounding variable of genetically determined gender. Experiments have shown that the temperature experienced during incubation plays a critical role in establishing the adult morphological, endocrinological, and behavioral phenotype. In this experiment, the independent effects of incubation temperature and gonadal sex on the morphology and metabolic capacity of specific brain nuclei were determined. Both individual and sex differences in the volume of the preoptic area and ventromedial nucleus of the hypothalamus are determined primarily by incubation temperature, not by gonadal sex. However, incubation temperature and gonadal sex are both important in determining the metabolic capacity in the anterior hypothalamus, external amygdala, dorsal lateral nucleus of the hypothalamus, dorsal lateral nucleus of the thalamus, dorsal ventricular ridge, habenula, lateral hypothalamus, nucleus rotundus, nucleus sphericus, periventricular nucleus of the hypothalamus, preoptic area, periventricular nucleus of the preoptic area, septum, striatum, torus semicircularis, and ventromedial nucleus of the hypothalamus. This is the first demonstration in a vertebrate that factors other than gonadal sex hormones, which arise from the individual's genetic constitution, can affect the sexual differentiation of the brain.

Animals↗

Species diversity and the evolution of behavioral controlling mechanisms.

One of the first things that we are impressed by is the great variety of animals, particularly their behaviors and their physiologies. With so many differences, are there any generalities? With the establishment of evolutionary theory, evidence of "unity in diversity" comes with discoveries of common anatomical features, the cell cycle, conservation of intermediary metabolism, and the genetic code, to name but a few. In vertebrates there appears to be a conservation of the neural circuits underlying sexual behavior, but it is still too early to state the extent to which this concept can be extended to the hormonal mechanisms underlying behavior. Much of our conceptual understanding of behavioral neuroendocrinology stems from extensive studies on relatively few species. When an evolutionary perspective is applied to behavioral neuroscience, the breadth and validity of our assumptions about the mechanisms that control species-typical behaviors are challenged. This is not the same thing as saying that there are few unitary explanations that apply to all mammals, amniotes, or even vertebrates. Considerable information has been gathered about the neuroendocrine bases of behavior in a few species, but to uncover truly broad generalizations, we must look with equal intensity and rigor at other organisms. The pattern of evolution is best illustrated in the diversity of organisms, and the ecological and evolutionary perspective illuminates the utility of various "experiments of nature." By studying (1) closely related species that live in different habitats, we can see if the adaptational responses are similar, and (2) distantly related species that live in the same habitat, we can see if the solutions are analogous. The unique qualities of each species also give us a deeper understanding of the constraints in fundamental processes. When basic conflicts exist, control mechanisms adapt or the species goes extinct. Interestingly, although the neural circuits themselves do not degenerate, they are either no longer used or coopted for other functions.

Animals↗

Effects of intrauterine position on the metabolic capacity of the hypothalamus of female gerbils.

The intrauterine position that a rodent fetus occupies relative to members of the same or opposite gender affects both its reproductive physiology and behavior when adult. Cytochrome oxidase histochemistry was used to assess regional differences in the oxidative metabolic capacity of the hypothalamus of female Mongolian gerbils that developed in utero between 2 female fetuses (n = 15) or between 2 male fetuses (n = 14). Cytochrome oxidase reactivity was measured densitometrically by experimenters unaware of subject intrauterine position. Gray-to-white matter ratios of optical density in 11 brain regions were used as a normalized index of metabolic capacity. Significant group differences in the metabolic capacity of the medial and the posterior parts of the anterior hypothalamus were revealed. Females that developed in utero between 2 male fetuses showed significant increases (19-22%) in cytochrome oxidase reactivity in these brain regions compared to that in females that developed between 2 female fetuses. The medial part of the anterior hypothalamus contributes to copulatory behavior, whereas the posterior part of the anterior hypothalamus may be involved in the control of pituitary gonadotropin secretion. Both these functions are influenced by intrauterine position during fetal life. To our knowledge, this is the first demonstration of metabolic changes in hypothalamic areas of the adult related to the differences in intrauterine position.

Animals↗

Sex differences in the nervous system of reptiles.

1. The study of sex differences in the brain and behavior of reptiles presents an excellent opportunity both to discern general principles of sexual differentiation in the nervous system and to explore the evolutionary history of this process in amniote vertebrates. 2. Findings in several reptiles suggest that some sex differences found in mammals and birds are conserved while others are not. Conserved features include areas in the limbic forebrain involved in the regulation of social and sexual behaviors. As in mammals and birds, it is rare to find differences in the distribution of sex steroid concentrating neurons in reptiles but common to find differences in the distribution of the various steroid hormone receptors and in their regulation. 3. This research has revealed that differences in social and sexual behavior are reflected better by the activity, not by the size, of hormone-sensitive limbic areas. 4. Finally, species differences in plasma levels of sex hormones are paralleled by differences in behavioral sensitivity to these hormones as well as by differences in the regulation of genes coding for steroid hormone receptors.

Animals↗

Behavioural sex change in the absence of gonads in a coral reef fish.

It is an axiom of vertebrate behavioural endocrinology that full expression of a male behavioural phenotype depends on testicular influences during development, in adulthood, or both. Sex change in fishes challenges this necessity: behavioural changes are often rapid and greatly precede gonadal changes. However, steroid hormones can have fast actions on the nervous system, so gonadal influences on behavioural sex change cannot be excluded based solely on the speed of these changes. We report that surgical gonad removal does not prevent or discernibly alter female-to-male behavioural sex change in a protogynous coral reef fish. Male behaviour assumption is instead purely dependent on attaining social dominance. This is the first example of a vertebrate fully expressing a male behavioural phenotype without current or previous exposure to a functioning testis or testicular products.

Animals↗

Intrahypothalamic implantation of progesterone in castrated male whiptail lizards (Cnemidophorus inornatus) elicits courtship and copulatory behavior and affects androgen receptor- and progesterone receptor-mRNA expression in the brain.

A primary tenet of behavioral neuroendocrinology is that gonadal steroid hormones act on limbic nuclei to activate mating behavior in vertebrates. Traditionally, research has focused on the regulation of male-typical sexual behavior by testicular androgens and female-typical sexual behavior by ovarian estrogen and progesterone. Indeed, progesterone generally is regarded as an antiandrogen, acting centrally to inhibit sexual behavior in males. However, experiments with lizards, and more recently with rats, have challenged this paradigm. For example, exogenous progesterone induces mating behavior in some, but not all, castrated male whiptail lizards. The present study determined that implantation of progesterone into the anterior hypothalamus preoptic area of castrated, progesterone-sensitive males completely restored sexual behavior but failed to elicit sexual activity in castrated, progesterone-insensitive males. Further, androgen receptor -and progesterone receptor-mRNA expression in specific brain regions was significantly different in progesterone-sensitive versus progesterone-insensitive animals. Progesterone-sensitive males showed significantly higher relative abundance of androgen receptor-mRNA in the preoptic area, amygdala, and lateral septum, as compared with progesterone-insensitive animals receiving the same treatment. In contrast, progesterone receptor-mRNA abundance was lower in preoptic area of progesterone-sensitive males than in progesterone-insensitive males. No differences were found in the baseline abundance of androgen receptor-or progesterone receptor-mRNA in these nuclei between control groups of progesterone-sensitive and progesterone-insensitive males who were castrated but not implanted. This suggests that progesterone differentially regulates its own receptor as well as androgen receptor in areas of the brain involved in the control of sexual behavior of males and that the nature of this regulation shows individual variability.

Amygdala↗

Pinealectomy, melatonin, and courtship behavior in male red-sided garter snakes (Thamnophis sirtalis parietalis).

Activation of courtship behavior in male red-sided garter snakes is independent of androgens. Only exposure to extended periods of low temperature with subsequent warming stimulates courtship in males. The pineal gland is thought to transduce temperature as well as photoperiodic information in reptiles. Therefore, we explored the relationship of the pineal and melatonin to sexual behavior in this species. Pinealectomy of male garter snakes disrupted sexual behavior upon emergence from a 17-week period of low temperature in approximately 60% of treated individuals in each of the 3 years of study. However, 40% of the males were unaffected by the pinealectomy, engaging in vigorous courtship. Administration of exogenous, chronic melatonin did not significantly modulate the effect of pinealectomy. Upon pinealectomy in the autumn (before hibernation), plasma levels of melatonin fell. However, upon emergence from hibernation, melatonin levels in pinealectomized (PINX) and sham-treated (SHAM) animals were equivalent, indicating extrapineal source(s) of melatonin. However, PINX males did not exhibit a diel cycle in melatonin levels upon emergence. Instead, melatonin remained elevated through the subsequent 24-hr period. SHAMs did exhibit a diel cycle. Ten days after emergence, PINX animals either had a disrupted/abnormal melatonin cycle and were non-courters or had a cycle similar to SHAM males and courted. Therefore, a normal diel cycle of melatonin appeared necessary for the proper expression of courtship behavior. These results suggest that the pineal in snakes 1) is part of a complex, multi-oscillator system as it is in birds and lizards and 2) may play a role in maintaining polymorphism in timing of reproductive behavior.

Acclimatization↗

The relative effectiveness of estrone, estradiol-17 beta, and estriol in sex reversal in the red-eared slider (Trachemys scripta), a turtle with temperature-dependent sex determination.

In many turtles the temperature during the middle of incubation determines the gonadal sex of the hatchling. Sex steroid hormones have been implicated in temperature-dependent sex determination in the red-eared slider turtle, Trachemys scripta; nonaromatizable androgens are involved in male sex determination and estrogens and aromatizable androgens in female sex determination. Administration of exogenous estradiol-17 beta to eggs incubating at a temperature that normally produces only males can overcome the effect of temperature and result in all offspring being female. Further, estradiol-17 beta and incubation temperature synergize to produce a greater feminizing effect at intermediate incubation temperatures that produce mixed sex ratios. This study demonstrates that, in the red-eared slider, there is a complex interaction between incubation temperature, different estrogens, and the dosage effect of each hormone. There are changes in potency of different estrogens with incubation temperature such that estriol is more potent than estrone and estradiol-17 beta at 26 degrees (an all-male producing incubation temperature), estrone and estriol are equipotent to each other and more potent than estradiol-17 beta at 28.8 degrees (an incubation temperature that produced a male-biased sex ratio), and estradiol-17 beta is more potent than estrone and estriol at 29 degrees (an incubation temperature that produced equal numbers of males and females). These changes may be due to differences in synergism between the hormones and incubation temperature. Estriol treatment also resulted in cranially hypertrophied oviducts at all incubation temperatures in a dose-dependent manner, whereas animals treated with estradiol-17 beta and estrone had normal oviducts. These results support the hypothesis that estrogens are involved in the final common pathway of female sex determination in this species.

Animals↗

Progesterone inhibits female-typical receptive behavior and decreases hypothalamic estrogen and progesterone receptor messenger ribonucleic acid levels in whiptail lizards (genus Cnemidophorus).

Female-typical sexual behavior in tetrapods is mediated primarily by estrogen and progesterone acting through intracellular receptors at specific sites in the mediobasal hypothalamus. Progesterone exerts both faciliatory and inhibitory actions on female sexual behavior and in well-studied rodent models, the inhibitory actions are exerted through downregulation of progesterone and estrogen receptors. This study examined progesterone effects on both female-typical sexual behavior and hypothalamic estrogen and progesterone receptor mRNA expression (ER- and PR-mRNA) in a sexual and parthenogenetic species of whiptail lizard. Progesterone capsules administered to ovariectomized female Cnemidophorus inornatus and Cnemidophorus uniparens following a receptivity-inducing dosage of estradiol benzoate (EB) strongly inhibited receptive behavior as compared to blank implanted controls. Progesterone capsules administered either before or after an EB injection also strongly downregulated ER- and PR-mRNA abundance in the ventromedial nucleus of the hypothalamus relative to blank implanted controls. The correlated decrease in both EB-induced receptive behavior and ER- and PR-mRNAs following progesterone administration are similar to findings in rats and guinea pigs, suggesting that this is an evolutionarily conserved mechanism in the regulation of female sexual behavior.

Animals↗

Courting and noncourting male red-sided garter snakes, Thamnophis sirtalis parietalis: plasma melatonin levels and the effects of pinealectomy.

Previous studies found that pinealectomy of male Canadian red-sided garter snakes (Thamnophis sirtalis parietalis) in the autumn, before prolonged exposure to low temperatures (hibernation), significantly impaired the expression of courtship behavior upon emergence in the spring. Additionally, pinealectomized animals with a disrupted diel cycle of plasma melatonin did not court while those exhibiting a more typical diel pattern did. These results suggested that the pineal gland functions in the transduction of a temperature cue which stimulates courtship. To test this hypothesis, we pinealectomized males in the spring after they had undergone a normal hibernation but were still courting. Pinealectomy of courting males in the spring, in each of the 3 years of study, had no effect on courtship. This result suggests that once the cue is transduced, the pineal gland no longer has a modulatory effect on courtship behavior. Finally, we took advantage of the fact that, in the laboratory, there is always a small percentage of males that do not court upon emergence. Pinealectomy of these noncourters greatly increased the percent of males expressing courtship behavior in each of the study years. Plasma melatonin levels of unmanipulated courting and noncourting males was measured after emergence in successive years. In both years, courters had a typical pattern of melatonin secretion (low in the photophase, high in the scotophase) while persistent noncourters displayed the opposite pattern.

Animals↗