Direct evidence in men for a role of endogenous oestrogens on gonadotrophin release

D’Agata, Rosario; Vicari, Enzo; Aliffi, A.; Gulizia, S.; Palumbo, Giuseppe

doi:10.1530/acta.0.0970145

Cited by 21 publications

(7 citation statements)

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“…Recently, a neural deficiency in P450 AROM activity was found in long-term castrated monkey that was shown to be associated with T-insensitivity (Resko et al, 2000b). Taken together, these data are consistent with experimental studies performed on human subjects, which have also suggested that endogenous estrogen inhibits gonadotropin release in men (Santen, 1981;D'Agata et al, 1981). Moreover, the endocrine evaluation of men that are either P450 AROM deficient (Morishima et al, 1995;Carani et al, 1997) or estrogen resistant (Smith et al, 1994) due to genetic mutations reveals the presence of chronically elevated gonadotropins in these individuals, a finding that is indicative of a disrupted negative feedback mechanism.…”

supporting

confidence: 83%

Anatomic relationships between aromatase and androgen receptor mRNA expression in the hypothalamus and amygdala of adult male cynomolgus monkeys

Roselli

Klosterman

Resko

2001

J of Comparative Neurology

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This study mapped the regional locations of cells expressing cytochrome P450 aromatase (P450AROM) and androgen receptor (AR) mRNAs in the adult male macaque hypothalamus and amygdala by in situ hybridization histochemistry using monkey-specific cRNA probes. High densities of P450AROM and AR mRNA-containing neurons were observed in discrete hypothalamic areas involved in the regulation of gonadotropin secretion and reproductive behavior. P450AROM mRNA-containing neurons were most abundant in the medial preoptic nucleus, bed nucleus of the stria terminalis, and anterior hypothalamic area, whereas AR mRNA-containing neurons were most numerous in the ventromedial nucleus, arcuate nucleus, and tuberomamillary nucleus. Moderate to heavily labeled P450AROM mRNA-containing cells were present in the cortical and medial amygdaloid nuclei, which are known to have strong reciprocal inputs with the hypothalamus. Heavily labeled P450AROM mRNA-containing cells were found in the accessory basal amygdala nucleus, which projects to the cingulate cortex and hippocampus, areas that are important in the expression of emotional behaviors and memory processing. In contrast to P450AROM, the highest density of AR mRNA labeling in the temporal lobe was associated with the cortical amygdaloid nucleus and the pyramidal cells of the hippocampus. All areas that contained P450AROM mRNA-expressing cells also contained AR mRNA-expressing cells, but there were areas in which AR mRNA was expressed but not P450AROM mRNA. The apparent relative differences in the expression of P450AROM and AR mRNA-containing neurons within the monkey brain suggests that T acts through different signaling pathways in specific brain areas or within different cells from the same region.

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supporting

confidence: 83%

Anatomic relationships between aromatase and androgen receptor mRNA expression in the hypothalamus and amygdala of adult male cynomolgus monkeys

Roselli

Klosterman

Resko

2001

J of Comparative Neurology

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“…The estimated MCRonRit under normal conditions agree well with the results of Tharandt et al [2], Under tamoxifen, in men the MCR decreased significantly, but serum lev els of LH and testosterone changed slightly, in contrast to D'Agata et al [20] and Vermeulen and Comhaire [21] who found more pronounced increases in gonadotropin, tes tosterone and also estradiol levels after ta moxifen administration. Whereas changes of testosterone may be caused by tamoxifen in fluence on serum sex-hormonc-binding glob ulin, the free fraction of testosterone in our study excludes that the tamoxifen-induced decrease in the MCR is related to an increase in testosterone levels.…”

Section: Discussionsupporting

confidence: 88%

“…Our data -increased basal values of LH under tamoxifen in 7 of 9 men and in women -and the augmented gonadotropin secretion after GnRH in men [20,21 ] and in women [16] may be related to a decrease in the MCR(lnRH as a consequence of estrogen blockade; thus, GnRH concentrations are in creased and pituitary' gonadotropin secretion is stimulated. Furthermore, it seems to be conceivable that an enhanced metabolism of GnRH may contribute to the known nega tive estrogenic feedback on the secretion of gonadotropins [19,22,23].…”

Section: Discussionmentioning

confidence: 56%

“…Furthermore, exogenous es trogens reduce the GnRH-stimulated gonad otropin response in men and in women dur ing the follicular phase [17][18][19]. In contrast, tamoxifen causes a significant increase in the secretion of LH and FSH after GnRH [16,20,21]. We administered 20 mg tamoxifen daily which is known to be the minimal effective dose [6], although this effect was not documented in the present study.…”

Section: Discussionmentioning

confidence: 89%

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Metabolism of GnRH in Man: Influence of Estrogens

Cissewski¹,

Tharandt²,

Benker³

et al. 1987

Horm Res

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To clarify the influence of estrogens on the metabolism of gonadotropin-releasing hormone (GnRH), we studied the metabolic clearance rate (MCR) of GnRH (MCRgnrh), and the serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol and testosterone (total and free fraction) in 9 sexually mature men and 7 women under basal conditions and after treatment with the antiestrogen tamoxifen (2 × 10 mg/day p.o.) for 7 days. In women, the medication was started on day 7 ± 1 of their menstrual cycles. To calculate the MCR, synthetic GnRH was continuously infused (1.53 µg/min) and its serum levels were measured by a radioimmunoassay. During tamoxifen treatment we observed a small but significant decrease in the MCR in men (455 ± 48 to 357 ± 46 ml/min/1.86 m²), whereas the known cyclic increase in the MCR in women was blunted (1,769 ± 147 to 1,558 ± 119 ml/min/1.86 m²). There was a small but significant increase in LH levels in women (8.3 ± 2.1 to 11.5 ± 2.5 mU/ml). LH and testosterone levels in men, and FSH and estradiol levels in both sexes did not change significantly. Conclusion: (1) estrogens regulate the MCRg_GnRH either directly or by changing gonadotropin levels, but the effect is only slight; (2) an enhanced metabolism of GnRH may contribute to the feedback of estrogens on the secretion of gonadotropins, and (3) the sex-specific difference of the MCR is presumably not caused by estrogens.

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“…D'Aga'te et a1. 6 reported that a fall in estrogen levels after hydrotestolactone induced a significant increase in serum LH and FSH.…”

Section: Discussionmentioning

confidence: 99%

Alteration of the Hypothalamus‐pituitary‐testis Axis in Oligozoospermic Men With Normal Gonadotropin Levels

Fujisawa¹,

Kanzaki²,

Hayashi³

et al. 1995

Int J of Urology

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Direct evidence in men for a role of endogenous oestrogens on gonadotrophin release

Cited by 21 publications

References 0 publications

Anatomic relationships between aromatase and androgen receptor mRNA expression in the hypothalamus and amygdala of adult male cynomolgus monkeys

Anatomic relationships between aromatase and androgen receptor mRNA expression in the hypothalamus and amygdala of adult male cynomolgus monkeys

Metabolism of GnRH in Man: Influence of Estrogens

Alteration of the Hypothalamus‐pituitary‐testis Axis in Oligozoospermic Men With Normal Gonadotropin Levels

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