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Biomedical subjects

D Crews

Publications and source records attributed to D Crews.

At least 91 records · Page 5Linked to original sources
PubMed1995

The role of estrogen in turtle sex determination and the effect of PCBs.

In the current model of vertebrate sex determination and sexual differentiation, gonadal sex is fixed at fertilization by specific chromosomes, a process known as genotypic sex determination (GSD). Only after the gonad is formed do hormones begin to exert an influence that modifies specific structures that eventually will differ the sexes. Many egg-laying reptiles do not exhibit GSD but rather depend on the temperature of the incubating egg to determine the gonadal sex of the offspring, a process termed temperature-dependent sex determination (TSD). Research on TSD indicates that sex determination in these species is fundamentally different in at least one way. Gonadal sex is not irrevocably set by the genetic composition inherited at fertilization but depends ultimately on which genes encoding for steroidogenic enzymes and hormone receptors are activated during the midtrimester of embryonic development by temperature. Incubation temperature modifies the activity as well as the temporal and spatial sequence of enzymes and hormone receptors such that sex-specific hormone milieus, created in the urogenital system of the developing embryo, determine gonad type. Estrogen is the physiologic equivalent of incubation temperature and the proximate cue that initiates female sex determination. There is increasing evidence that some polychlorinated biphenyl (PCB) compounds are capable of disrupting reproductive and endocrine function in fish, birds, and mammals, including humans. Reproductive disorders resulting from exposure to these xenobiotic compounds may include reductions in fertility, hatch rate in fish and birds, and viability of offspring, as well as alterations in hormone levels or adult sexual behaviors, all of which have further implications, particularly in wildlife population dynamics. Research on the mechanism through which these compounds may be acting to alter reproductive function indicates estrogenic activity, by which the compounds may be altering sexual differentiation. In TSD turtles, the estrogenic effect of some PCBs reverses gonadal sex in individuals incubating at an otherwise male-producing temperature. Furthermore, certain PCBs are synergistic in their effect at very low concentrations.

Animals↗
PubMed1994

The bisexual brain: sex behavior differences and sex differences in parthenogenetic and sexual lizards.

The parthenogenetic lizard Cnemidophorus uniparens alternates in the display of male-like and female-like sexual behavior, providing a unique opportunity for determining the neuronal circuits subserving gender-typical sexual behavior within a single sex. Here we report a 6-fold greater [14C]2-fluoro-2-deoxyglucose uptake in the medial preoptic area of C. uniparens displaying male-like behavior in comparison with C. uniparens displaying female-like receptivity. The ventromedial nucleus of the hypothalamus showed greater 2DG accumulation in receptive C. uniparens than in courting C. uniparens. When a related sexual species (C. inornatus) was compared to the unisexual species, the anterior hypothalamus in C. inornatus males exhibited significantly greater activity.

Animals↗
PubMed1994

Cloning and in situ hybridization analysis of estrogen receptor, progesterone receptor, and androgen receptor expression in the brain of whiptail lizards (Cnemidophorus uniparens and C. inornatus).

Gonadal steroid hormones act upon specific areas of the vertebrate brain to affect the reproductive physiology and behavior of the animal. Steroid receptors are members of a superfamily of ligand-dependent transcription factors that mediate the effects of steroid hormones by modulating gene expression in the cells containing the receptors. The neuroanatomical distributions of steroid receptor-containing cells have been described for several species by using steroid autoradiography, immunocytochemistry, and more recently in situ hybridization. We have used the polymerase chain reaction to amplify and clone fragments of the estrogen receptor, progesterone receptor, and androgen receptor of whiptail lizards (genus Cnemidophorus). These clones were used to produce probes for use in in situ hybridization assays and to map the neuroanatomical distribution of all three sex steroid hormone receptors in the forebrains of unisexual (C. uniparens) and sexual (C. inornatus) species of whiptail lizards. The distribution of receptor-expressing cells reported here is in general agreement with previous reports in other species with receptor-containing cells concentrated in septal, amygdaloid, cortical, preoptic, and hypothalamic nuclei.

Animals↗
PubMed1994

Effects of hypothalamic lesions on courtship and copulatory behavior in sexual and unisexual whiptail lizards.

Lesions of the anterior hypothalamus-medial preoptic area (AH-MPOA) impair courtship and copulatory behavior in male Cnemidophorus inornatus, a sexually reproducing species of whiptail lizard, and male-like pseudosexual behaviors in C. uniparens, an all-female species. These results suggest that, since C. inornatus is a direct ancestor to C. uniparens, the neural structures responsible for mediating male-typical courtship and copulatory behavior in male whiptails are conserved in the evolution of the all-female parthenogen.

Animals↗
PubMed1994

Effect of exogenous estradiol applied at different embryonic stages on sex determination, growth, and mortality in the leopard gecko (Eublepharis macularius).

Temperature-dependent sex determination (TSD) occurs in three orders of reptiles. Several studies have examined the ability of estradiol to produce female hatchlings incubated at a male-producing temperature. The results of these experiments support the idea that estradiol could be used as a powerful tool in the conservation of endangered species with TSD by manipulating hatchling sex ratios. However, these experiments have concentrated on the mechanism of determination. This experiment was designed to test the efficacy of various dosages of estradiol applied at two different stages to alter the hatchling sex ratio as well as determining the potential use of such manipulation for conservation efforts by monitoring egg mortality and hatchling growth. The leopard gecko (Eublepharis macularius) exhibits TSD and reaches reproductive maturity in less than one year, making it an excellent model for evaluating the long-term effects of estradiol. The results demonstrate that estradiol has a dose-dependent effect on the hatchling sex ratio while only high dosages applied at the later stage of development showed increased mortality. Estrogen-determined females grew at the same rate as temperature-determined females and have produced viable hatchlings. Estradiol treatment of eggs from endangered species may provide a method of insuring female offspring when the TSD pattern is unknown or equipment for controlled incubation is unavailable.

Animals↗
PubMed1994

Temperature-dependent sex determination in reptiles: proximate mechanisms, ultimate outcomes, and practical applications.

In many egg-laying reptiles, the incubation temperature of the egg determines the sex of the offspring, a process known as temperature-dependent sex determination (TSD). In TSD sex determination is an "all or none" process and intersexes are rarely formed. How is the external signal of temperature transduced into a genetic signal that determines gonadal sex and channels sexual development? Studies with the red-eared slider turtle have focused on the physiological, biochemical, and molecular cascades initiated by the temperature signal. Both male and female development are active processes--rather than the organized/default system characteristic of vertebrates with genotypic sex determination--that require simultaneous activation and suppression of testis- and ovary-determining cascades for normal sex determination. It appears that temperature accomplishes this end by acting on genes encoding for steroidogenic enzymes and steroid hormone receptors and modifying the endocrine microenvironment in the embryo. The temperature experienced in development also has long-term functional outcomes in addition to sex determination. Research with the leopard gecko indicates that incubation temperature as well as steroid hormones serve as organizers in shaping the adult phenotype, with temperature modulating sex hormone action in sexual differentiation. Finally, practical applications of this research have emerged for the conservation and restoration of endangered egg-laying reptiles as well as the embryonic development of reptiles as biomarkers to monitor the estrogenic effects of common environmental contaminants.

Amino Acid Sequence↗
PubMed1994

Incubation temperature affects the behavior of adult leopard geckos (Eublepharis macularius).

The leopard gecko has temperature-dependent sex determination (TSD); females are predominantly produced when incubated at 26 degrees C (100%), 30 degrees C (70%), and 34 degrees C (95%), whereas males are predominantly produced at 32.5 degrees C (75%). Exogenous estradiol can override the effect of temperature on sex determination. To compare temperature-determined females with hormone-determined females, eggs from the male-biased temperature were treated with estradiol benzoate during incubation. As adults, animals from a male-biased incubation temperature were more likely to exhibit aggression than animals from female-biased incubation temperatures. Furthermore, females from a male-biased incubation temperature tended to be less attractive than females from female-biased temperatures. Hormone-determined females were both attractive and aggressive. This suggests that incubation temperature is an important development determinant of adult aggressiveness and attractiveness. The 26 degrees C animals ovariectomized on the day of hatch exhibited more frequent aggression and were unreceptive to males, indicating that postnatal ovarian hormones also play a role in adult sociosexual behaviors. The parallel between incubation temperature and intrauterine position in laboratory mammals is discussed.

Aggression↗
PubMed1994

Progesterone and sexual behavior in males.

Previous investigations into the effects of progestins on copulatory behavior have suggested that progesterone inhibits the expression of androgen-dependent sexual behaviors in males. However, virtually all of those studies utilized pharmacological dosages of progesterone. Such experiments, although essential for understanding the behavioral effects of progesterone, yield little insight into the function of endogenous progesterone in masculine sexual responses. In this brief review, attention is focused on the role of physiological levels progesterone in copulatory behavior in male reptiles and mammals. Efforts are made to promote a reevaluation of the behavioral effects of progestins in males, similar to ongoing studies which are reexamining neural mechanisms involved in progestin-mediated reproductive behavior in the female.

Animals↗
PubMed1994

PCBs as environmental estrogens: turtle sex determination as a biomarker of environmental contamination.

Polychlorinated biphenyls (PCBs) are widespread, low-level environmental pollutants associated with adverse health effects such as immune suppression and teratogenicity. There is increasing evidence that some PCB compounds are capable of disrupting reproductive and endocrine function in fish, birds, and mammals, including humans, particularly during development. Research on the mechanism through which these compounds act to alter reproductive function indicates estrogenic activity, whereby the compounds may be altering sexual differentiation. Here we demonstrate the estrogenic effect of some PCBs by reversing gonadal sex in a reptile species that exhibits temperature-dependent sex determination.

Animals↗
PubMed1994

Putative aromatase inhibitor induces male sex determination in a female unisexual lizard and in a turtle with temperature-dependent sex determination.

Treatment of developing embryos of two diverse species of reptiles with fadrozole (a potent and specific nonsteroidal inhibitor of aromatase activity in mammals) resulted in the induction of male sex determination. In the first experiment, males were produced in an all-female parthenogenic species of lizard (Cnemidophorus uniparens). In the second experiment, male sex determination was induced in a turtle (Trachemys scripta) with temperature-dependent sex determination. The results support the hypothesis that the endogenous production of oestrogen may represent a pivotal step in the sex determination cascade of reptiles. Further, the production of male C uniparens indicates that the genes required for male sexual differentiation have not been lost in this parthenogenic lizard.

Animals↗
PubMed1994

Role of reductase and aromatase in sex determination 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. In the red-eared slider turtle (Trachemys scripta), an incubation temperature of 26 degrees C results in all male offspring, whereas an incubation temperature of 31 degrees C results in all female offspring; at temperatures intermediate to these (e.g. 29, 29.2, 29.4 degrees C) a mixed sex ratio is obtained. Administration of exogenous oestrogens will overcome the effects of an all-male producing incubation temperature to cause female sex determination, whereas administration of exogenous dihydrotestosterone (DHT) or testosterone to eggs incubating at an all-female temperature will have no discernible effect. Administration of DHT will cause male sex determination only if administered at intermediate incubation temperatures whereas administration of testosterone to eggs incubating at all male-producing and male-biased intermediate temperatures results in a significant number of female offspring, an effect presumably due to aromatization of testosterone to oestradiol (OE2). Since testosterone serves as the precursor to both DHT and OE2, being metabolized by reductase and aromatase respectively, three experiments were conducted to determine whether various putative reductase and aromatase inhibitors would overcome the effect of incubation temperature. First, while administration of testosterone to eggs incubating at all male-producing and male-biased intermediate temperatures produced females in a dose- and temperature-dependent manner, significant numbers of intersex individuals resulted from high dosage testosterone treatment to eggs incubating at a female-biased intermediate temperature. The reductase inhibitors 4MA and MK906 were capable of producing female offspring if administered at intermediate temperatures, but not in a dose-dependent fashion. Administration of the aromatase inhibitors CGS16949A and CGS20267 resulted in male offspring at both female-biased intermediate and at all female-producing temperatures in a dose-dependent fashion. Second, similar findings were obtained with combined doses of testosterone and reductase or aromatase inhibitors. Combined treatment of eggs at male-biased intermediate incubation temperatures with testosterone and reductase inhibitor resulted in female hatchlings, whereas combined treatment of testosterone and aromatase inhibitor at both female-biased intermediate and at all female-producing temperatures resulted in male hatchlings.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Identification of an isoform of the estrogen receptor messenger RNA lacking exon four and present in the brain.

An isoform of the estrogen receptor messenger RNA (ER-mRNA) was identified in RNA from the brain of lizards and rats. Poly(A)+ RNA from brain and uteri was reverse transcribed using gene-specific primer for the ER. The resulting complementary DNA was amplified in a polymerase chain reaction followed by cloning and sequencing of the amplified products. This isoform lacks exon four and is designated delta 4 ER-mRNA. Although several isoforms of the ER have been described from cancerous cells, to our knowledge, none has been identified previously in the brain. Furthermore, the delta 4 isoform is the only isoform detected in normal tissue. The delta 4 isoform appeared most abundant in RNA from brain tissue, whereas uterine RNA contained only trace amounts of the isoform. Apparently, tissue-specific alternative splicing accounts for these differences in abundance. Because exon four encodes a part of the steroid-binding domain, we predict that the corresponding protein encoded by the isoform will not bind estradiol and may therefore belong to a growing subclass of the steroid/thyroid/vitamin superfamily known as orphan receptors. We predict that the putative delta 4 protein may function as a ligand-independent transcription factor that acts on the same DNA response elements as the conventional ER. The abundance of this isoform in the brain relative to the uterus raises fundamental questions regarding the regulation of estrogen-responsive genes in different tissues.

Animals↗
PubMed1993

Temperature-dependent sex determination in the leopard gecko, Eublepharis macularius.

The leopard gecko, Eublepharis macularius, has temperature-dependent sex determination (TSD). Previous reports have shown that females are produced predominantly at cool incubation temperatures and males are produced predominantly at warm incubation temperatures (Pattern Ib). We report here that incubation at even higher temperatures (34 and 35 degrees C) produces mostly females (Pattern II). The lethal maximum constant incubation temperature for this species appears to be just above 35 degrees C. Although a previous study indicated that females from a warm incubation temperature (32 degrees C) failed to lay eggs, we found that 12 of 14 mature females incubated at 32.5 degrees C, and 5 of 6 mature females incubated at 34 degrees C produced fertile eggs and viable hatchlings.

Animals↗
PubMed1993

Androgen mediated effects of male fetuses on the behavior of dams late in pregnancy.

Two correlational studies were undertaken to explore the relationship between the sex ratio of the pups that a female Mongolian gerbil gestated and her behavior, morphology, and hormone levels late in pregnancy. In the first study, we found that the change in sex ratio between the first and second litters that a female gerbil delivered and the change in her frequency of scent marking late in her first and second pregnancies were significantly correlated. In the second study, we found significant positive correlations between both the percentage and the number of males in the litter a female delivered and (1) her plasma testosterone levels, (2) the size of her ventral gland, and (3) her frequency of scent marking, all measured late in pregnancy. Our data were entirely consistent with the hypothesis that fetal males excrete biologically significant quantities of testosterone into their dam's bloodstream and that this testosterone masculinizes both the behavior and morphology of dams late in pregnancy.

Androgens↗
PubMed1993

Effects of progesterone and dihydrotestosterone on stimulation of androgen-dependent sex behavior, accessory sex structures, and in vitro binding characteristics of cytosolic androgen receptors in male whiptail lizards (Cnemidophorus inornatus).

Progestins often act as potent antiandrogens in male birds and mammals. Experiments with lizards find that progestins can both inhibit (when given in high dosages) or stimulate (when given in low dosages) male-typical sex behavior in gonadectomized individuals. This study shows that in the little striped whiptail lizard exogenous progesterone (P) facilitates androgen-dependent sex behaviors in males yet fails to stimulate seasonal activation of androgen-dependent accessory sex structures. Analysis of androgen receptors (AR) in brain and kidney cytosol of the little striped whiptail lizard reveals similarities with the AR of the mouse. The data indicate that despite the ability of P to mimic the actions of androgens in activating sex behaviors in males of this species, the characteristics of the AR are conserved with respect to other vertebrate species.

Animals↗
PubMed1993

Hormonal control of sex differences in the brain, behavior and accessory sex structures of whiptail lizards (Cnemidophorus species).

The effects of steroid hormones on sexual dimorphisms in the brain, behavior and accessory sex structures were investigated in two species of whiptail lizards. The studies were conducted both in adults and hatchlings of a sexually reproducing species (Cnemidophorus inornatus) and an all-female species (C. uniparens) which displays 'sexual' behaviors typical of males and females. Adults were gonadectomized and approximately 3 months later given either a Silastic capsule filled with sex steroid or an empty capsule. Young animals of both species were left intact and given a capsule on the day of hatching. An additional group of C. uniparens was ovariectomized on the day of hatching. Following treatment, measures of oviduct (estrogen-dependent), renal sex segment (androgen-dependent) and wolffian duct (androgen-dependent) hypertrophy were taken in some experiments. Animals were also tested for sexual behavior in some of the studies. The volumes of the anterior hypothalamus-preoptic area and ventromedial hypothalamus were measured in each individual. Estrogen, testosterone and dihydrotestosterone stimulated peripheral structures at both time periods in both sexes and species. The hormones also stimulated courtship and copulatory behaviors in many of the adult animals. However, testosterone in the anterior hypothalamus-preoptic area of male C. inornatus was the only treatment which produced parallel effects on the volume of a brain area and the behaviors which it controls. These data add whiptail lizards to the list of species in which steroid hormones affect the volume of brain regions in adulthood, but suggest that such changes in morphology are not necessarily predictive of functional differences.

Animals↗