Androgen effects on hippocampal CA1 spine synapse numbers are retained in Tfm male rats with defective androgen receptors.
نویسندگان
چکیده
The effects of estradiol benzoate (EB), dihydrotestosterone (DHT), or the antiandrogen hydroxyflutamide on CA1 pyramidal cell dendritic spine synapses were investigated in adult male rats. To elucidate the contribution of the androgen receptor to the hormone-induced increase in hippocampal CA1 synapses, wild-type males were compared with males expressing the Tfm mutation, which results in synthesis of defective androgen receptors. Orchidectomized rats were treated with EB (10 microg/rat.d), DHT (500 mug/rat.d), hydroxyflutamide (5 mg/rat.d), or the sesame oil vehicle sc daily for 2 d and examined using quantitative electron microscopic stereological techniques, 48 h after the second injection. In wild-type males, DHT and hydroxyflutamide both induced increases in the number of spine synapses in the CA1 stratum radiatum, whereas EB had no effect. DHT almost doubled the number of synaptic contacts observed, whereas hydroxyflutamide increased synapse density by approximately 50%, compared with the vehicle-injected controls. Surprisingly, in Tfm males, the effects of EB, DHT, and hydroxyflutamide were all indistinguishable from those observed in wild-type animals. These observations demonstrate that Tfm male rats resemble normal males in having no detectable hippocampal synaptic response to a dose of EB that is highly effective in females. Despite the reduction in androgen sensitivity as a result of the Tfm mutation, hippocampal synaptic responses to both DHT and a mixed androgen agonist/antagonist (hydroxyflutamide) remain intact in Tfm males. These data are consistent with previous results suggesting that androgen effects on hippocampal spine synapses may involve novel androgen response mechanisms.
منابع مشابه
Gonadal hormones affect spine synaptic density in the CA1 hippocampal subfield of male rats.
The effects of androgen on the density of spine synapses on pyramidal neurons in the CA1 area of the hippocampus were studied in male rats. Gonadectomy (GDNX) had no significant effect on the number of CA1 pyramidal cells but reduced CA1 spine synapse density by almost 50% (to 0.468 +/- 0.018 spine synapses/microm(3)) compared with sham-operated controls (0.917 +/- 0.06 spine synapses/microm(3)...
متن کاملEffects of dehydroepiandrosterone and flutamide on hippocampal CA1 spine synapse density in male and female rats: implications for the role of androgens in maintenance of hippocampal structure.
The effects of androgens and the androgen antagonist, flutamide, on the density of dendritic spine synapses in the CA1 subfield of the hippocampus were studied in gonadectomized male and female rats. Treatment of orchidectomized male rats with dehydroepiandrosterone (DHEA; 2 d, 1 mg/d sc) increased the density of CA1 spine synapses observed 2 d later, by 106%, without significantly affecting ve...
متن کاملAndrogens increase spine synapse density in the CA1 hippocampal subfield of ovariectomized female rats.
The effects of androgen on the density of spine synapses on pyramidal neurons in the CA1 area of the hippocampus were studied in ovariectomized (OVX) adult female rats. Treatment of OVX rats with testosterone propionate (TP; 500 microg/d, s.c., 2 d) significantly increased spine synapse density (from 0.661 +/- 0.016 spine synapse/microm3 in OVX rats to 1.081 +/- 0.018 spine synapse/microm3 afte...
متن کاملEffects of androgens and estradiol on spine synapse formation in the prefrontal cortex of normal and testicular feminization mutant male rats.
Recent studies suggest that, in female monkeys and rats, estrogens elicit dendritic spine synapse formation in the prefrontal cortex, an area that, similar to the hippocampus, plays a critical role in cognition. However, whether gonadal hormones induce synaptic remodeling in the male prefrontal cortex remains unknown. Here we report that gonadectomy reduced, whereas administration of 5alpha-dih...
متن کاملIntrahippocampal Injection of 3α Diol (a Testosterone Metabolite ) and Indomethacin (3α-HSD Blocker), Impair Acquisition of Spatial Learning and Memory in Adult Male Rats
Hippocampus is essentially involved in learning and memory processes, and is known to be a target for androgen actions. The high density of the androgen receptors in hippocampus shows that there must be some relationship between androgens and memory. Androgen effects on spatial memory are complex and contradictory. Some evidence suggests a positive correlation between androgens and spatial memo...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Endocrinology
دوره 147 5 شماره
صفحات -
تاریخ انتشار 2006