Effect of Testosterone on Hypothalamic LH-RH Content
37
Citation
0
Reference
10
Related Paper
Abstract:
Hypothalamic LH-RH content in male rats is lowered after castration. The s.c. implantation of testosterone or testosterone propionate-packed Silastic tubing (from 0.5 to 6 cm in length) in a range which encompassed the normal circulating plasma testosterone concentration, prevented this lowered LH-RH content 21 days following castration and simultaneous implantation. The temporal response to implanted testosterone was then studied: rats were killed 1,2,4,8,14 and 21 days after castration and simultaneous implantation of 3 cm testosterone-packed Silastic tubing. The hypothalamic LH-RH content began to decrease in the castrated group after 4 days and fell progressively thereafter. However, the hypothalamic LH-RH content of the castrated group maintained with constant levels of testosterone showed no such reduction at any time following castration. These experiments indicate that circulating testosterone in physiological concentrations can maintain a normal hypothalamic LH-RH content and demonstrate an action of testosterone, in physiological concentrations, in the feedback regulation of LH-RH secretion.Keywords:
Testosterone propionate
Silastic
Serum LH changes in response to LH-RH injection were measured in intact and ovariectomized, steroid-treated female rats which were androgenized neonatally with 1,250 microgram testosterone propionate (TP) on day 5. At a dose of 20 ng LH-RH/100 g b.w., serum LH levels in intact rats increased over pre-injection levels, and at a dose of 100 ng LH-RH/100 g b.w., LH concentrations 15 min after injection were higher in nembutal-blocked proestrous rats than in androgen-sterilized rats. However, the ovulation response was not different between the groups. In ovariectomized estradiol benzoate (EB)-treated, androgen-sterilized rats, serum LH concentrations 15 and 60 min after LH-RH injection were lower than in similarly treated control rats. This effect was not secondary to the anovulatory state of the animal, since it also occurred in ovariectomized EB-treated prepuberal rats and in rats ovariectomized prepuberally and treated with EB in adulthood. Also, after treatment with 5alpha-dihydrotestosterone propionate (5alpha-DHTP), pituitary responsiveness to LH-RH in androgen-sterilized rats was lower than in control rats, which suggests that the subnormal response in the estrogen-treated rats was not due to a relative insensitivity to estrogen in the androgen-sterilized rats. The relatively high pituitary responsiveness to LH-RH in intact androgen-sterilized rats is probably due to the high circulating estrogen levels. The subnormal pituitary responsiveness to LH-RH after ovariectomy and estradiol treatment suggests, in addition to an effect on the hypothalamus, also a direct effect of neonatal androgen administration on the pituitary.
Testosterone propionate
Cite
Citations (4)
Ovarian steroids have previously been shown to regulate the hypothalamic content of β-endorphin (βEP) and its release into hypophyseal portal blood. Although the hypothalamic content of βEP in cycling female rats was unchanged by ovariectomy, chronic treatment of ovariectomized rats with estradiol lowered hypothalamic βEP levels. In this study, the hypothalamic content of βEP was compared in male and cycling female rats, and the effects of orchiectomy and testosterone replacement on hypothalamic βEP were examined. The j8EP content of the medial basal hypothalamus (MBH) was significantly higher in female rats compared to that in males of either the same weight (175–200 g) or the same age (65 days; P < 0.025). When male rats were studied 4 weeks after castration, the β-EP content of the MBH increased from a value of 2100 ± 103 fmol in the controls to 2680 ±126 fmol (P < 0.005). The hypothalamic βEP content in the castrated males was similar to that in the intact females (2700 ± 158 fmol). The increase in hypothalamic 0EP induced by castration was blocked by testosterone replacement. When orchiectomized animals were treated for 4 weeks with Silastic capsules filled with testosterone, there was a significant fall in the hypothalamic content of j8EP compared to that in the unreplaced animals. βEP fell from 3180 ± 115 to 2033 ± 53 fmol in the MBH (P < 0.001), from 1693 ± 122 to 934 ± 80 fmol in the anterior hypothalamus (P < 0.001), and from 148 ± 26 to 90.3 ±11 fmol in the median eminence (P < 0.05). Testosterone replacement was also associated with a significant decline in the hypothalamic content of corticotropinlike intermediate lobe peptide and aMSH. Corticotropin-like intermediate lobe peptide fell from 2400 ± 53 to 1560 ± 84 fmol in the MBH (P < 0.001) and from 1200 ± 74 to 805 ± 94 fmol in the anterior hylpothalamus (P < 0.01). aMSH fell from 1660 ± 162 to 884 ± 75 fmol in the MBH (P < 0.001) and from 823 ± 106 to 544 ± 92 fmol in the anterior hypothalamus (P < 0.05). Thus, testosterone, as well as estradiol, affects the hypothalamic content of several proopiomelanocortin-derived peptides. The effect on brain peptide content, however, depends on whether the steroids are secreted relatively constantly, as in the male, or fluctuate, as in the cycling female. (Endocrinology119: 19–24, 1986)
Median eminence
Orchiectomy
Silastic
Cite
Citations (48)
Studies were performed with the primary objective of evaluating the hypothesis that the onset of puberty in males is related to a change in the sensitivity of the negative feedback mechanisms which mediate the androgen suppression of LH secretion. Unlike previous studies, stabilized testosterone (T) levels were produced by sc implantation of Silastic capsules containing T, and both plasma T and LH were directly measured by RIA. Male rats were castrated and simultaneously received capsule implants at 26, 55 and 115 days of age, and autopsied 5 days later. A given level of plasma T produced a significantly greater suppression of plasma LH in the prepuberal than in the two older groups. It was concluded that the sensitivity of the testosterone-LH feedback mechanism is higher before than after puberty. A clear trend to increases of LH over the castrate control levels was found in castrated puberal rats treated with low T doses, but this stimulatory effect was not replicated in subsequent experiments. In addition, neither intact nor castrated puberal males showed diurnal variations in plasma LH levels. With increasing age, Silastic capsules of smaller surface area (adjusted for body weight) were required to produce a given T level, suggesting a progressive, age-related decrease in clearance of T from the circulation. When the mean plasma T level in groups of intact rats was reproduced by Silastic capsules following castration, it was found that the same plasma T level was more effective in suppressing LH and stimulating sexual accessory glands. One interpretation of this finding is that the natural pulsatile form of testicular androgen secretion results in a reduced biological effectiveness.
Silastic
Dihydrotestosterone
Plasma levels
Sexual maturity
Cite
Citations (56)
ABSTRACT Changes in the hypothalamic contents of LHRH-I and LHRH-II were determined in intact and castrated cockerels injected i.m. with gonadal steroids or tamoxifen. An increase in the plasma concentration of LH after castration was accompanied by a significant increase in the content of LHRH-I in the posterior hypothalamus (including the mediobasal hypothalamus and median eminence) which was reversed by oestradiol benzoate given on days 14 and 15 after castration. Under similar circumstances, testosterone propionate did not modify the hypothalamic content of LHRH-I, even though both steroids reduced the plasma concentrations of LH to levels below those of intact cockerels. Treatment of intact cockerels with oestradiol benzoate significantly increased the content of LHRH-I in the posterior hypothalamus, whilst testosterone propionate was again without effect. Tamoxifen significantly raised the plasma concentration of LH in intact cockerels and partially antagonized the suppressive effect of oestradiol benzoate and testosterone on LH secretion in castrated cockerels. However, an anti-oestrogenic effect of tamoxifen on the hypothalamic content of LHRH-I was not demonstrated. There was no evidence of any changes in the hypothalamic content of LHRH-II after castration, with or without gonadal steroid replacement. A change in the hypothalamic content of LHRH-I in response to manipulation of the steroid environment would imply an involvement of this peptide in the mechanism by which gonadal steroids regulate the release of LH. The absence of changes in the hypothalamic content of LHRH-II in the same circumstances suggest that it is not directly involved in the control of LH secretion by the gonadal steroid negative feedback loop. Journal of Endocrinology (1990) 125, 139–146
Testosterone propionate
Median eminence
Cite
Citations (21)
Since intact adult male rats have higher GH pulse amplitude than do castrated animals and since GH-releasing hormone (GHRH) secretion is predominantly responsible for the production of these GH pulses, we hypothesized that testosterone stimulates GHRH synthesis in neurons of the hypothalamus. To test this hypothesis, we compared GHRH mRNA content in individual neurons of the arcuate (ARC) and ventromedial (VMH) nuclei among groups of intact (n = 3), castrated (n = 5), and castrated testosterone-replaced (n = 5) adult male rats. Cellular GHRH mRNA content was measured by using semiquantitative in situ hybridization with an 35Slabeled cRNA probe complementary to the coding sequence of rat GHRH mRNA. Castration resulted in an approximately 35% decline in GHRH mRNA signal relative to that in intact animals in both the ARC (P < 0.005) and VMH (P < 0.005). Replacement with testosterone at the time of castration completely prevented the decline in both areas. Testosterone can exert effects either through activation of the androgen receptor directly or through aromatization to estradiol; therefore, we also examined the effects on GHRH mRNA of replacement with 17/3-estradiol (n = 5) or dihydrotestosterone (DHT), a nonaromatizable androgen (n = 4). Estradiol had no effect on the castration-induced decline in GHRH mRNA in either the ARC or VMH. In contrast, DHT partially prevented the postcastration decline in GHRH in the ARC (P < 0.005), while having no statistically significant effect on GHRH mRNA in the VMH. These results clearly indicate that testosterone stimulates expression of GHRH mRNA in neurons of the hypothalamus. Furthermore, the failure of estradiol to substitute for testosterone and the ability of DHT to substantially support GHRH mRNA suggest that testosterone exerts its effects on GHRH gene expression predominantly through direct activation of the androgen receptor. (Endocrinology127: 1362–1368, 1990)
Dihydrotestosterone
Cite
Citations (127)
High plasma levels of PRL induced by transplants of two donor pituitaries under the kidney capsule of adult male rats resulted in a prolonged suppression of plasma levels of LH and FSH although testosterone levels were maintained within normal limits. Castration of rats with pituitary transplants resulted in a normal though delayed rise in serum levels of both LH and FSH to levels equivalent to those in normal castrated controls. This increase in gonadotropin levels occurred in spite of maintenance of elevated PRL levels. Two experiments were carried out in which testosterone was restored after castration by Silastic testosterone-containing implants of various lengths (Exp 1:60, 30, and 10 mm; Exp 2: 30, 20, 10, 5, and 2 mm). In both experiments 60- and 30-mm testosterone implants prevented the postcastration rise in LH and FSH in both control and hyperprolactinemic rats. However, although the shorter testosterone implants delayed this rise in control rats, levels of LH and FSH increased by 4 days and were not significantly different from castrated rats without testosterone implants by 15 days after castration. In contrast, this rise in gonadotropins was abolished or considerably delayed by the shorter implants in hyperprolactinemic rats, demonstrating an increase in sensitivity of the hypothalamic pituitary axis to the negative feedback effects of testosterone in these animals. These results suggest that 1) to maintain suppression of gonadotropin secretion in hyperprolactinemia high levels of PRL alone are insufficient and gonadal steroids are required, and 2) high levels of PRL appear to sensitize the hypothalamic-pituitary axis to the negative feedback effects of gonadal steroids.
Silastic
Gonadotropin
Cite
Citations (32)
ABSTRACT Castration of male rats decreases both pituitary and serum TSH-levels. Administration of testosterone propionate increases serum TSH-levels in castrated males, but its effect on pituitary TSH-content appears to be complex: whereas treatment with physiological amounts of testosterone prevents the decrease induced by castration, administration of high doses of testosterone results in low pituitary TSH-contents not unlike those seen in untreated castrated rats. Testosterone administered to thyroxine-maintained thyroidectomized rats had the same effects as mentioned above, but if thyroxine treatment was omitted, no effect of testosterone on pituitary and serum TSH-levels could be observed. It is thought that testosterone interferes with the effect of thyroid hormone on the secretion of TSH.
Testosterone propionate
Cite
Citations (16)
Testosterone propionate
Cite
Citations (5)
The effect of castration (CAS), hypophysectomy (HYPOX), and gonadal steroids on hypothalamic luteinizing hormone-releasing hormone (LHRH) content was studied in male and female rats. Hypothalamic LHRH content was significantly reduced by 1 week after castration in male rats and was further reduced by 2 weeks. HYPOX decreased LHRH content in male rats to the same extent as in CAS rats alone, suggesting that loss of gonadal function was mainly responsible for the fall in hypothalamic LHRH in these rats. In castrated male rats testosterone propionate (TP) at a dose of 0.5 mg/300 g body weight raised hypothalamic LHRH content above that of intact rats and reduced serum LH below the intact level. However, in castrated-hypophysecto-mized rats, TP treatment only returned hypothalamic LHRH content to the intact level.
Testosterone propionate
Hypophysectomy
Adult male
Cite
Citations (18)