Ontogeny of serum and pituitary gonadotrophins in male rats treated with low doses of 5α-dihydrotestosterone

Karanth, Sharada; gill, Mc; Dutt, A.; Lehri, N.; Juneja, H. S.

doi:10.1677/joe.0.1080369

“…Male mice with targeted disruption of the nNOS gene (nNOS Ϫ ) display a great increase in aggressive behavior and excessive and inappropriate mounting behavior (11). Because androgens also promote aggressive behavior (23,24), facilitate mounting behavior (25,26), and decrease gonadotropin release (27,28), we wanted to elucidate whether the androgens, testosterone (T) and its 5␣ reduced metabolite, dihydrotestosterone (DHT), modulate nNOS activity in the brain and the potential mechanism(s) by which this may occur.…”

mentioning

confidence: 99%

Castration increases and androgens decrease nitric oxide synthase activity in the brain: Physiologic implications

Singh¹

2000

Proceedings of the National Academy of Sciences

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Sex differences in nitric oxide synthase (NOS) activity in different regions of the rat brain and effects of testosterone and dihydrotestosterone (DHT) treatment in orchidectomized animals were investigated. Regional but no sex differences in NOS activity were detected in gonadectomized animals. Orchidectomy significantly increased NOS activity in the hypothalamus, ''amygdala,'' and cerebellum but not in the cortex. In the hypothalamus, the increase in NOS activity after castration and its reversal by androgen treatment was mimicked by changes in neuronal NOS mRNA level. In contrast, androgen receptor (AR) mRNA level in the hypothalamus was slightly reduced by castration and increased by treatment with DHT. Again in the hypothalamus, the increase in NOS activity in castrated rats was accompanied by an increase in the number of neuronal NOS؉ cells determined immunohistochemically, whereas androgen treatment prevented this increase. The changes in NOS؉ neurons correlated with the changes in the number of AR؉ cells to a degree. Overlap of AR in NOS؉ cells was not present in the regions of the hypothalamus analyzed. These results indicate that testosterone or, most likely, its metabolite DHT down-regulates NOS activity, mRNA expression or stabilization, and the number of neuronal NOS؉ neurons. N itric oxide (NO) synthesized by the enzyme neuronal nitric oxide synthase (nNOS) plays an important role in many brain functions. These include effects on long-term potentiation (1), gonadotropin secretion (2-10), and sexual behavior (11)(12)(13). NO functions as a neurotransmitter (2-10) and nNOS is present near gonadotropin-releasing hormone terminals (14) and in regions of the brain that appear to regulate emotional behaviors (15, 16). Estradiol (E 2 ) up-regulates endothelial NOS in endothelial cells (17,18) and nNOS in the brain (18-21), and many of the actions of E 2 on the brain have been suggested to be through a NO-mediated mechanism (2-10, 18-22). Administration of E 2 and progesterone to ovariectomized rats leads to an increase in the luteinizing hormone surge, the magnitude of which is significantly attenuated after administration of nNOS antisense oligonucleotides into the third ventricle (22), suggesting an intermediary role of NO in modulating some actions of E 2 by up-regulating nNOS activity.However, the actions of androgens on NOS activity in the brain are not clear. Male mice with targeted disruption of the nNOS gene (nNOS Ϫ ) display a great increase in aggressive behavior and excessive and inappropriate mounting behavior (11). Because androgens also promote aggressive behavior (23, 24), facilitate mounting behavior (25, 26), and decrease gonadotropin release (27, 28), we wanted to elucidate whether the androgens, testosterone (T) and its 5␣ reduced metabolite, dihydrotestosterone (DHT), modulate nNOS activity in the brain and the potential mechanism(s) by which this may occur.Therefore, sex-related and region-specific distributions of NOS in select regions of the rat brain of both sexes were assessed as ...

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“…As the study was of 46 days' duration, the animals advanced in age from day 75 to day 121. The serum levels of LH, FSH and PRL could be affected by the age of the animals (16)(17)(18)(19). Age-matched intact rats were therefore killed along with every castrated group.…”

Section: Discussionmentioning

confidence: 99%

“…The levels of LH, FSH and PRL are low in CSF. Since three different hormones were to be assayed in duplicate, it became necessary to pool CSF from at least [15][16][17][18][19][20] rats to obtain CSF adequate for the study (around 3 ml). Data when pooled for analysis contained at least three such pools for each day postcastration.…”

Section: Collection Of Csfmentioning

confidence: 99%

Cerebrospinal fluid and blood concentrations of luteinizing hormone, follicle stimulating hormone and prolactin following castration of adult male rats

Balasinor

¹

,

Gill-Sharma²,

Parte³

et al. 1992

Acta Endocrinologica

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Comparative levels of LH, FSH and PRL in the serum and cerebrospinal fluid (CSF) of adult male rats were studied at different periods following castration. Intact and sham-operated animals served as controls. Blood and CSF were collected at 1, 3, 7, 14, 21, 28, 35 and 46 days following castration. The CSF was collected via cisterna-magna puncture, while the blood was collected from abdominal aorta. Serum gonadotropins increased progressively beginning day 1 post-castration to reach maximum by day 35 or 46 post-castration. Sham operation and castration did not affect mean CSF, LH and FSH levels compared to intact controls. Analysis of the temporal pattern of serum and CSF gonadotropin levels following castration revealed significant positive correlation between CSF and serum LH (r=0.58) and FSH (r=0.64) levels respectively. The data suggest that CSF gonadotropins may be derived from systemic circulation. Serum PRL levels were not affected by castration, but CSF PRL levels were significantly reduced at days 28, 35 and 46 post-castration compared to intact controls. CSF PRL levels showed negative correlation with serum LH and FSH levels but failed to show a correlation with serum PRL levels. Hypothalamic norepinephrine turnover rate increased at days 28, 35 and 46 post-castration. Hypothalamic dopamine contents and turnover rates were reduced at days 21 and 28 post-castration. It is suggested that CSF PRL may have a role in the regulation of serum gonadotropins.

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Castration increases and androgens decrease nitric oxide synthase activity in the brain: Physiologic implications

Singh¹,

Pervin²,

Shryne³

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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Sex differences in nitric oxide synthase (NOS) activity in different regions of the rat brain and effects of testosterone and dihydrotestosterone (DHT) treatment in orchidectomized animals were investigated. Regional but no sex differences in NOS activity were detected in gonadectomized animals. Orchidectomy significantly increased NOS activity in the hypothalamus, ''amygdala,'' and cerebellum but not in the cortex. In the hypothalamus, the increase in NOS activity after castration and its reversal by androgen treatment was mimicked by changes in neuronal NOS mRNA level. In contrast, androgen receptor (AR) mRNA level in the hypothalamus was slightly reduced by castration and increased by treatment with DHT. Again in the hypothalamus, the increase in NOS activity in castrated rats was accompanied by an increase in the number of neuronal NOS؉ cells determined immunohistochemically, whereas androgen treatment prevented this increase. The changes in NOS؉ neurons correlated with the changes in the number of AR؉ cells to a degree. Overlap of AR in NOS؉ cells was not present in the regions of the hypothalamus analyzed. These results indicate that testosterone or, most likely, its metabolite DHT down-regulates NOS activity, mRNA expression or stabilization, and the number of neuronal NOS؉ neurons. N itric oxide (NO) synthesized by the enzyme neuronal nitric oxide synthase (nNOS) plays an important role in many brain functions. These include effects on long-term potentiation (1), gonadotropin secretion (2-10), and sexual behavior (11)(12)(13). NO functions as a neurotransmitter (2-10) and nNOS is present near gonadotropin-releasing hormone terminals (14) and in regions of the brain that appear to regulate emotional behaviors (15, 16). Estradiol (E 2 ) up-regulates endothelial NOS in endothelial cells (17,18) and nNOS in the brain (18-21), and many of the actions of E 2 on the brain have been suggested to be through a NO-mediated mechanism (2-10, 18-22). Administration of E 2 and progesterone to ovariectomized rats leads to an increase in the luteinizing hormone surge, the magnitude of which is significantly attenuated after administration of nNOS antisense oligonucleotides into the third ventricle (22), suggesting an intermediary role of NO in modulating some actions of E 2 by up-regulating nNOS activity.However, the actions of androgens on NOS activity in the brain are not clear. Male mice with targeted disruption of the nNOS gene (nNOS Ϫ ) display a great increase in aggressive behavior and excessive and inappropriate mounting behavior (11). Because androgens also promote aggressive behavior (23, 24), facilitate mounting behavior (25, 26), and decrease gonadotropin release (27, 28), we wanted to elucidate whether the androgens, testosterone (T) and its 5␣ reduced metabolite, dihydrotestosterone (DHT), modulate nNOS activity in the brain and the potential mechanism(s) by which this may occur.Therefore, sex-related and region-specific distributions of NOS in select regions of the rat brain of both sexes were assessed as ...

show abstract

Ontogeny of serum and pituitary gonadotrophins in male rats treated with low doses of 5α-dihydrotestosterone

Cited by 3 publications

References 28 publications

Castration increases and androgens decrease nitric oxide synthase activity in the brain: Physiologic implications

Castration increases and androgens decrease nitric oxide synthase activity in the brain: Physiologic implications

Cerebrospinal fluid and blood concentrations of luteinizing hormone, follicle stimulating hormone and prolactin following castration of adult male rats

Castration increases and androgens decrease nitric oxide synthase activity in the brain: Physiologic implications

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