Biomedical subjects

K K Soma

Publications and source records attributed to K K Soma.

17 recordsLinked to original sources

PubMed2006

Testosterone and aggression: Berthold, birds and beyond.

Berthold's classic study of domesticated roosters in 1849 demonstrated that testicular secretions are necessary for the normal expression of aggressive behaviour. Although this conclusion is undoubtedly correct, field studies of wild songbirds have yielded important modifications and limitations of Berthold's original hypothesis. For example, studies of the North American song sparrow (Melospiza melodia) during the breeding season reveal that not only does testosterone increase aggression, but aggressive interactions also increase plasma testosterone levels. Furthermore, in winter, nonbreeding song sparrows have low plasma testosterone levels but are very aggressive, and castration of nonbreeding song sparrows does not decrease aggression. Interestingly, an aromatase inhibitor (fadrozole) does decrease male aggression in the nonbreeding season, and the effects of fadrozole can be rescued with oestradiol. In winter, dehydroepiandrosterone (DHEA) from the periphery can be metabolised within the brain to supply oestradiol to specific neural circuits. Additionally, oestradiol might be synthesised de novo from cholesterol entirely within the brain. These mechanisms may have evolved to avoid the 'costs' of circulating testosterone in the nonbreeding season. Recent studies in tropical birds, hamsters, and humans suggest that these neuroendocrine mechanisms are important for the control of aggression in many vertebrate species.

Aggression↗

PubMed2005

Neurosteroids and female reproduction: estrogen increases 3beta-HSD mRNA and activity in rat hypothalamus.

A central event in mammalian reproduction is the LH surge that induces ovulation and corpus luteum formation. Typically, the LH surge is initiated in ovariectomized rats by sequential treatment with estrogen and progesterone (PROG). The traditional explanation for this paradigm is that estrogen induces PROG receptors (PR) that are activated by exogenous PROG. Recent evidence suggests that whereas exogenous estrogen is necessary, exogenous PROG is not. In ovariectomized-adrenalectomized rats, estrogen treatment increases hypothalamic PROG levels before an LH surge. This estrogen-induced LH surge was blocked by an inhibitor of 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase (3beta-HSD), the proximal enzyme for PROG synthesis. These data indicate that estrogen induces de novo synthesis of PROG from cholesterol in the hypothalamus, which initiates the LH surge. The mechanism(s) by which estrogen up-regulates neuro-PROG is unknown. We investigated whether estrogen increases 1) mRNA levels for several proteins involved in PROG synthesis and/or 2) activity of 3beta-HSD in the hypothalamus. In ovariectomized-adrenalectomized rats, estrogen treatment increased 3beta-HSD mRNA in the hypothalamus, as measured by relative quantitative RT-PCR. The mRNAs for other proteins involved in steroid synthesis (sterol carrier protein 2, steroidogenic acute regulatory protein, and P450 side chain cleavage) were detectable in hypothalamus but not affected by estrogen. In a biochemical assay, estrogen treatment also increased 3beta-HSD activity. These data support the hypothesis that PROG is a neurosteroid, produced locally in the hypothalamus from cholesterol, which functions in the estrogen positive-feedback mechanism driving the LH surge.

Animals↗

PubMed2001

Hippocampal volume does not change seasonally in a non food-storing songbird.

Seasonal differences in hippocampal morphology have been reported in food-storing birds. Non food-storing species have not been investigated however. It is therefore unclear whether seasonal changes in the hippocampus are specifically related to food-storing or reflect a more general seasonal mechanism that occurs in both food-storing and non food-storing birds alike. We determined the volumes of the hippocampal formation and remaining telencephalon in the non-storing male song sparrow (Melospiza melodies morphna) in two experiments comparing birds collected in the spring and fall of 1992-94 (Experiment 1) and 1997 (Experiment 2). Although pronounced seasonal changes in song control nuclei such as the HVC and RA were previously reported for the same brains used in Experiment 1, we found that hippocampal volume did not change with season in either Experiment 1 or 2 for these song sparrow brains. These results suggest that seasonal changes in the hippocampus do not occur in this non food-storing species and may be specific to food-storing birds.

Animals↗

PubMed2001

Dehydroepiandrosterone in songbird plasma: seasonal regulation and relationship to territorial aggression.

Many male animals are territorial in the breeding season, when plasma testosterone (T) levels are high, and nonterritorial in the nonbreeding season, when plasma T levels are basal. In contrast to this common pattern, male song sparrows (Melospiza melodia morphna) are territorial year-round, except briefly during molt. Song sparrows are highly aggressive in the nonbreeding season (autumn and winter), even though plasma T, 5 alpha-dihydrotestosterone, androstenedione (AE), and 17beta-estradiol levels are undetectable (<or=0.1 ng/ml). Castration has no effect on nonbreeding territoriality. However, aromatase inhibitors decrease aggression in the nonbreeding season, indicating a role for estrogens in winter. The androgenic substrate for brain aromatase in winter is unclear, because plasma T and AE levels are basal. Here, we measured plasma levels of dehydroepiandrosterone (DHEA). DHEA is a precursor to AE and T, and the avian brain can convert DHEA into sex steroids. In nonbreeding male song sparrows, plasma levels of DHEA were detectable and several times higher than plasma AE and T levels. Plasma DHEA levels were similar in the breeding and nonbreeding seasons, but significantly lower during molt, which parallels seasonal changes in male aggression. Adrenal glands and testes from nonbreeding males had high concentrations of DHEA, suggesting that both tissues may secrete DHEA. However, stress and gonadotropin-releasing hormone (GnRH) did not increase plasma DHEA in nonbreeding birds. We hypothesize that in the nonbreeding season, circulating DHEA, possibly of adrenal origin, is converted into active sex steroids by steroidogenic enzymes in the brain. This mechanism would create high local levels of sex steroids in the brain to support winter aggression.

Adrenal Glands↗

PubMed2001

Neurosteroids and brain sexual differentiation.

There is new evidence that the brain of developing songbirds can synthesize estradiol de novo. In males, this neurally derived estrogen might masculinize a connection within the neural song system. These results challenge traditional concepts about mechanisms of brain sexual differentiation and reveal a significant function for neurosteroids.

Animals↗

PubMed2001

Avoiding the 'costs' of testosterone: ecological bases of hormone-behavior interactions.

A combination of laboratory and field investigations of birds has shown that expression of behavior such as territorial aggression can occur throughout the year in many species and in different life history stages. Although it is well known that testosterone regulates territorial aggression in males during the breeding season, the correlation of plasma testosterone and aggression appears to be limited to periods of social instability when a male is challenged for his territory by another male, or when mate-guarding a sexually receptive female. How essentially identical aggression is modulated in non-breeding life history stages is not fully resolved, but despite low circulating levels of testosterone outside the breeding season, expression of territorial aggression does appear to be dependent upon aromatization of testosterone and an estrogen receptor-mediated mechanism. There is accumulating evidence that prolonged high levels of circulating testosterone may incur costs that may potentially reduce lifetime fitness. These include interference with paternal care, exposure to predators, increased risk of injury, loss of fat stores and possibly impaired immune system function and oncogenic effects. We propose six hypotheses to explain how these costs of high testosterone levels in blood may be avoided. These hypotheses are testable and may reveal many mechanisms resulting from selection to avoid the costs of testosterone. It should also be noted that the hypotheses are applicable to vertebrates in general, and may also be relevant for other hormones that have a highly specialized suite of actions in one life history stage (such as breeding), but also have a limited action in other life history stages when the full spectrum of effects would be inappropriate.

Aggression↗

PubMed2000

Oestrogen regulates male aggression in the non-breeding season.

Extensive research has focused on territorial aggression during the breeding season and the roles of circulating testosterone (T) and its conversion to 17beta-oestradiol (E2) in the brain. However, many species also defend territories in the non-breeding season, when circulating T-levels are low. The endocrine control of non-breeding territoriality is poorly understood. The male song sparrow of Washington State is highly territorial year-round, but plasma T is basal in the non-breeding season (autumn and winter). Castration has no effect on aggression in autumn, suggesting that autumnal territoriality is independent of gonadal hormones. However, non-gonadal sex steroids may regulate winter territoriality (e.g. oestrogen synthesis by brain aromatase). In this field experiment, we treated wild non-breeding male song sparrows with a specific aromatase inhibitor (fadrozole, FAD) using micro-osmotic pumps. FAD greatly reduced several aggressive behaviours. The effects of FAD were reversed by E2 replacement. Treatment did not affect body condition or plasma corticosterone, suggesting that all subjects were healthy These data indicate that E2 regulates male aggression in the non-breeding season and challenge the common belief that aggression in the non-breeding season is independent of sex steroids. More generally, these results raise fundamental questions about how sexual and/or aggressive behaviours are maintained in a variety of model vertebrate species despite low circulating levels of sex steroids or despite castration. Such non-classical endocrine mechanisms may be common among vertebrates and play an important role in the regulation of behaviour.

Aggression↗

PubMed2000

Testosterone and year-round territorial aggression in a tropical bird.

Testosterone (T) regulates avian behaviors such as song and aggression during the breeding season. However, the role of T in year-round territorial birds is still enigmatic, especially in tropical birds. Spotted antbirds (Hylophylax n. naevioides) defend territories in the Panamanian rainforest year-round but have low plasma T levels (0.1-0.2 ng/ml), except during brief periods of social challenges. We manipulated T action in captive male Spotted antbirds to test whether this hormone is involved in the regulation of song and aggression. T-implants increased plasma androgen levels (T and dihydrotestosterone) and enhanced song in nonbreeding males. During a staged male-male encounter, T-implanted males sang more and were more aggressive than controls. In a second experiment, we blocked the two known T actions: its binding to androgen receptors and its conversion into estradiol by the enzyme aromatase. For this, we administered the androgen receptor antagonist flutamide (Flut) in combination with the aromatase inhibitor 1-4-6 androstatrien-3, 17-dione (ATD) to birds in breeding condition. ATD + Flut treatment significantly elevated plasma levels of luteinizing hormone, presumably via the lack of T feedback from its receptors. ATD + Flut-treated birds gave fewer spontaneous songs than control-implanted males. During staged male-male encounters, ATD + Flut-treated males did not sing at all and showed reduced aggressive behavior. Our data indicate that T can regulate aggressive behavior in these tropical birds. Although plasma T levels can be low year-round, Spotted antbirds may use T either by secreting it briefly during social challenges, by having a high sensitivity to T action, or by enzymatically converting circulating T precursors directly at the site of action. We hypothesize that plasma T levels are kept low in these year-round territorial birds to avoid potentially detrimental effects of tonically elevated T. Future treatment of nonbreeding birds with ATD + Flut will reveal whether T is indeed involved year-round in regulating aggressive behavior.

Aggression↗

PubMed1999

Androgen-metabolizing enzymes show region-specific changes across the breeding season in the brain of a wild songbird.

The Lapland longspur (Calcarius lapponicus) is an arctic-breeding songbird that shows rapid behavioral changes during a short breeding season. Changes in plasma testosterone (T) in the spring are correlated with singing but not territorial aggression in males. Also, T treatment increases song but not aggression in this species. In contrast, in temperate-zone breeders, song and aggression are highly correlated, and both increase after T treatment. We asked whether regional or temporal differences in androgen-metabolizing enzymes in the longspur brain explain hormone-behavior patterns in this species. We measured the activities of aromatase, 5alpha-reductase and 5beta-reductase in free-living longspur males. Aromatase and 5alpha-reductase convert T into the active steroids 17beta-estradiol (E(2)) and 5alpha-dihydrotestosterone (5alpha-DHT), respectively. 5beta-Reductase deactivates T via conversion to 5beta-DHT, an inactive steroid. We examined seven brain regions at three stages in the breeding season. Overall, aromatase activity was high in the hypothalamus, hippocampus, and ventromedial telencephalon (containing nucleus taeniae, the avian homologue to the amygdala). 5beta-Reductase activity was high throughout the telencephalon. Activities of all three enzymes changed over time in a region-specific manner. In particular, aromatase activity in the rostral hypothalamus was decreased late in the breeding season, which may explain why T treatment at this time does not increase aggression. Changes in 5beta-reductase do not explain the effects of plasma T on aggressive behavior.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed1999

Seasonal changes in androgen receptor immunoreactivity in the song nucleus HVc of a wild bird.

In seasonally breeding songbirds, song behavior and neural morphology change seasonally. Song control nuclei are larger during the breeding season, as determined by multiple cytological labels. Seasonal changes in song nuclei are regulated by testosterone (T), and several song nuclei contain intracellular androgen receptors (AR). Changes in AR levels may interact with changes in plasma T levels to regulate song nuclei morphology. We measured seasonal changes in AR-immunoreactive cells in the telencephalic song nucleus HVc using the affinity-purified PG21 antibody to rat AR. We caught wild adult male Gambel's white-crowned sparrows (Zonotrichia leucophrys gambelii) during spring breeding in Alaska and during autumn migration in Washington State. To enhance PG21 labeling, animals were treated with T for 90 minutes (as in Smith et al. [1996] J. Histochem. Cytochem. 44:1075-1080). AR+ cells were found in HVc and other song nuclei, hippocampus, nucleus taeniae (homologue to mammalian amygdala), and the hypothalamus. HVc volume was larger in spring (S) than autumn (A), in both the PG21- and Nissl-stained sections (S:A = 1.9 and 1.7, respectively). In spring, but not autumn, PG21 and Nissl measurements were slightly different (PG21:Nissl = 1.07), perhaps because PG21 labeled the most caudal extent of HVc more clearly. In HVc, AR+ cell density and number were greater in spring. The percentage of AR+ cells was also increased in spring. Qualitatively, the staining intensity of individual cells was higher in spring. In time course studies, the T injection enhanced PG21 staining within 15 minutes, suggesting that it increases labeling via AR translocation to and concentration in the cell nucleus.

Animals↗

PubMed1999

Combined aromatase inhibitor and antiandrogen treatment decreases territorial aggression in a wild songbird during the nonbreeding season.

Male song sparrows (Melospiza melodia morphna) defend territories throughout the year in western Washington State. In the nonbreeding season (autumn and winter), aggression and song are robustly expressed but plasma testosterone (T) levels are basal. Also, castration does not decrease nonbreeding territoriality. In this field experiment, we asked whether nonbreeding aggression is independent of T. T can act via androgen receptors or T can be aromatized to 17beta-estradiol (E(2)) and act via estrogen receptors. We treated free-living nonbreeding birds with an aromatase inhibitor (ATD) and an androgen receptor antagonist (flutamide) in combination. We then challenged subjects with a live decoy and playback of tape-recorded songs. ATD+flutamide treatment decreased several aggressive behaviors. However, ATD+flutamide treatment did not affect body condition, suggesting that subjects were healthy and that foraging behavior was not reduced. As expected, ATD+flutamide treatment increased plasma T, probably by blocking negative feedback on luteinizing hormone. Surprisingly, ATD+flutamide treatment increased plasma E(2). Most other studies using aromatase inhibitors have not measured plasma E(2). However, it is possible that ATD+flutamide treatment decreased local E(2) levels in the brain but not in plasma. Finally, ATD+flutamide treatment increased plasma corticosterone, perhaps in response to increased plasma T or E(2). To our knowledge, these are the first data to suggest that nonbreeding territoriality is regulated by endogenous steroid hormones. Nongonadal production of sex steroids may support aggression in the nonbreeding season.

Aggression↗

PubMed1998

The hypothalamus and adrenal regulate modulation of corticosterone release in redpolls (Carduelis flammea--an arctic-breeding song bird).

Free-living redpolls (Carduelis flammea-a species that breeds in the Alaskan Arctic), modulate corticosterone release in response to capture and restraint depending upon the breeding site. We extended these findings to adults undergoing a prebasic molt (the energetically costly replacement of feathers) and to juveniles. Results indicate not only that the stress response is dramatically reduced at one breeding site, but that the stress response during molt and in juveniles is lower still. In fact, juveniles failed to secrete any corticosterone in response to capture and handling, suggesting a stress hyporesponsive period. We also examined possible mechanisms underlying stress modulation. Corticosterone binding protein capacity does not change, and the stress response is only correlated with the overall condition of the bird (assessed by fat storage) at one site, suggesting that neither can explain the different corticosterone responses. Adrenal insensitivity also does not appear to fully explain reduced maximal output since exogenous ACTH enhanced corticosterone release. Exogenous ACTH, however, cannot stimulate corticosterone to stress-induced levels at the high-response site, implying reduced adrenal capacity. Redpoll pituitaries responded to exogenous corticotrophin-releasing factor and arginine vasotocin, suggesting a mechanism upstream from the pituitary blunts corticosterone release. Taken together, these results indicate that corticosterone release in this species is modulated depending upon the ecological and physiological state of the animal, and that the maximal corticosterone response is controlled at multiple sites in the hypothalamic-pituitary-adrenal axis.

Adrenal Glands↗

PubMed1998

Hormones and territorial behavior during breeding in snow buntings (Plectrophenax nivalis): an Arctic-breeding songbird.

We examined hormonal profiles and behavior associated with maintaining a single-purpose territory in an Arctic-breeding songbird-the snow bunting (Plectrophenax nivalis). Snow buntings differ from many other Arctic-breeding passerines by using nest cavities, an uncommon and defended resource, but not relying upon the surrounding territory for forage. Circulating levels of testosterone in males were high when territories were established and then decreased over the breeding season. LH secretion was enhanced in females while laying eggs, followed by detectable levels of estradiol during incubation. Both sexes showed equivalent corticosterone responses to the stress of being captured and held. Male snow buntings vigorously defended territories in response to a simulated territorial intrusion both when initiating breeding and when feeding young. Exogenous testosterone implants surprisingly inhibited physical aggression but enhanced singing when birds were feeding young, thus suggesting that song and physical aggression are mediated by different hormonal mechanisms at this time of year. Together, these results contrast with hormonal profiles and behavior in other Arctic-breeding passerines.

Animals↗

PubMed1998

Changes in pituitary and adrenal sensitivities allow the snow bunting (Plectrophenax nivalis), an Arctic-breeding song bird, to modulate corticosterone release seasonally.

Several free-living avian species have recently been shown to seasonally modulate corticosterone release in response to capture and restraint. We examined possible mechanisms underlying seasonal adrenocortical modulation in snow buntings (Plectrophenax nivalis), a species that breeds and molts (the energetically costly replacement of feathers) in the Alaskan Arctic Snow buntings dramatically reduced baseline and maximal corticosterone titers during molt compared to the breeding season. This effect is not explained by changes in either corticosterone binding protein capacity or the overall condition of the bird (assessed by weight and fat storage). Although the adrenal's capacity to secrete corticosterone is reduced during molt, adrenal insensitivity does not fully explain reduced maximal output since exogenous adrenocorticotropic-hormone enhanced corticosterone release during both seasons. In contrast, no exogenous adrenocorticotropic hormone releasing factor (corticotrophin-releasing factor, arginine vasotocin or mesotocin) enhanced corticosterone secretion during molt. This suggests that the pituitary's endogenous adrenocorticotropic secretion was maximal in response to capture and handling, making the pituitary an important site regulating corticosterone levels. Taken together, these results indicate that seasonal modulation of corticosterone release in this species is controlled at both the adrenal and pituitary glands.

Adrenal Glands↗

PubMed1998

Hypothalamic-pituitary-adrenal axis changes allow seasonal modulation of corticosterone in a bird.

We examined possible mechanisms underlying seasonal stress modulation in Lapland longspurs (Calcarius lapponicus), a species that breeds and molts (the energetically costly replacement of feathers) in the Alaskan Arctic. Free-living Lapland longspurs show dramatically reduced maximal corticosterone release during molt compared with the breeding season, an effect lost in captive birds. Neither changes in corticosterone binding proteins nor the overall condition of the bird (assessed by weight and fat storage) can explain different seasonal corticosterone responses. Adrenal insensitivity also does not fully explain reduced maximal output because exogenous ACTH enhanced corticosterone release during molt. Exogenous ACTH in molting birds, however, cannot stimulate corticosterone to stress-induced levels during breeding, implying reduced adrenal capacity. Lapland longspur pituitaries appeared to respond to exogenous corticotropin-releasing factor, arginine vasotocin, and mesotocin (the avian equivalents of arginine vasopressin and oxytocin) during molt, suggesting that a mechanism upstream of the pituitary blunts corticosterone release. Taken together, these results indicate that seasonal modulation of corticosterone release in this species is controlled at multiple sites in the hypothalamic-pituitary-adrenal axis.

Animals↗

PubMed1996

Androgen regulation of hypothalamic neurons containing gonadotropin-releasing hormone in a cichlid fish: integration with social cues.

Reproduction in vertebrates is regulated by internal signals such as hormone levels and by external signals such as social interactions. In an African cichlid fish, Haplochromis burtoni, the effect of social interactions is evident in the hypothalamo-pituitary-gonadal (HPG) axis of males. Territorial males, characterized by aggressive and reproductive activity, have significantly larger hypothalamic gonadotropin-releasing hormone (GnRH)-containing neurons and larger testes than nonterritorial males. Furthermore, a switch in the social status of an adult male causes a corresponding change in GnRH neuron size and testis size. Here we show that the GnRH-containing neurons in the hypothalamus of adult territorial males are also influenced by gonadal hormones. Castration of territorial males caused GnRH neurons to increase in size. This neuronal hypertrophy in castrated animals was prevented either by testosterone (T) or 11-ketotestosterone (KT) treatment. Estradiol (E2) treatment did not reduce GnRH cell size in castrated animals. These results suggest that androgens reduce the size of GnRH cells through negative feedback. Since E2 had no effect, androgen influence on GnRH cell size appears to be independent of aromatization. These data are consistent with the hypothesis that the setpoint for hypothalamic GnRH cell size is determined by social cues and that this setpoint is maintained by negative feedback from gonadal androgens.

Androgens↗

PubMedDate not supplied

Acute and chronic effects of an aromatase inhibitor on territorial aggression in breeding and nonbreeding male song sparrows.

Many studies have demonstrated that male aggression is regulated by testosterone. The conversion of testosterone to estradiol by brain aromatase is also known to regulate male aggression in the breeding season. Male song sparrows (Melospiza melodia morphna) are territorial not only in the breeding season, but also in the nonbreeding season, when plasma testosterone and estradiol levels are basal. Castration has no effect on nonbreeding aggression. In contrast, chronic (10 day) aromatase inhibitor (fadrozole) treatment decreases nonbreeding aggression, indicating a role for estrogens. Here, we show that acute (1 day) fadrozole treatment decreases nonbreeding territoriality, suggesting relatively rapid estrogen effects. In spring, fadrozole decreases brain aromatase activity, but acute and chronic fadrozole treatments do not significantly decrease aggression, although trends for some behaviors approach significance. In gonadally intact birds, fadrozole may be less effective at reducing aggression in the spring. This might occur because fadrozole causes a large increase in plasma testosterone in intact breeding males. Alternatively, estradiol may be more important for territoriality in winter than spring. We hypothesize that sex steroids regulate male aggression in spring and winter, but the endocrine mechanisms vary seasonally.

Aggression↗