The effect of orchidectomy on rat pituitary responsiveness to GHRH depends on age

Pinilla, Leonor; Fj, López; Aguilar, E.

doi:10.1530/acta.0.1220349

Cited by 13 publications

(16 citation statements)

References 21 publications

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“…In contrast, response to GRF was fairly similar in young and middle-aged rats. In both age groups, the same dose of GRF induced an almost immediate release of pituitary growth hormone, although the magnitude of response may have been somewhat greater in the younger animals (Miki et al, 1984;Pinilla et al, 1990). Thus, changes in the sexually dimorphic plasma growth hormone profiles observed in middle age may be explained by a reduced ability of the hypothalamus to secrete GRF and, to a lesser extent, by a possible reduction in pituitary responsiveness to GRF.…”

mentioning

confidence: 92%

Middle-Age Alterations in the Sexually Dimorphic Plasma Growth Hormone Profiles: Involvement of Growth Hormone-Releasing Factor and Effects on Cytochrome P450 Expression

Dhir

Dworakowski²,

Shapiro³

2002

Drug Metab Dispos

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This paper is available online at http://dmd.aspetjournals.org ABSTRACT:Rat liver, as well as other species, contains numerous sex-dependent isoforms of cytochrome P450 (P450) that are regulated by the sexually dimorphic profiles of circulating growth hormone. During puberty, young adulthood, and senescence, changes in the hormonal profiles appear to be responsible for alterations in ageassociated expression levels of selective P450 isoforms. In contrast, little is known about the growth hormone secretory profiles and their P450-dependent expression levels during middle age. In the present study, we observed subtle changes in the hormonal concentrations, and frequencies of peaks and interpulse periods in the sexually dimorphic growth hormone profiles of 1-year-old male and female rats correlated to suppression of male-specific isoforms CYP2C11 and CYP2C13 and female-predominant CYP2C7. To identify possible causes for the age-associated changes in the circulating growth hormone profiles, the responsiveness of the hypothalamic-pituitary axis to growth hormone secretagogues clonidine and growth hormone-releasing factor (GRF) were examined in middle-aged male and female rats. In spite of the same sexually dimorphic response in young adult and middle-aged rats to both secretogogues (males > females), the pituitary somatotrophs in the older animals exhibited a dramatic decrease in sensitivity to clonidine, characterized by subnormal growth hormone release levels and an inordinate delay in pituitary response to clonidine stimulation. Results from similar studies conducted on middle-aged arcuate nucleus-lesioned rats suggest that a decline in GRF secretion is a possible contributor to the age-associated alterations in plasma growth hormone profiles during middle age. These changes in GRF-induced, sexually dimorphic secretory growth hormone profiles and the accompanying decline in P450 expression levels may anticipate similar, but more profound, changes to occur during senescence.

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mentioning

confidence: 92%

Middle-Age Alterations in the Sexually Dimorphic Plasma Growth Hormone Profiles: Involvement of Growth Hormone-Releasing Factor and Effects on Cytochrome P450 Expression

Dhir

Dworakowski²,

Shapiro³

2002

Drug Metab Dispos

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“…The effects of orchidectomy depended on the age at which it was performed: orchidectomy in adult hood reduced GH responsiveness, whereas the opposite effect was observed in prepubertal males [3], This differ ence was not due to the secretion of diols as principal androgens by prepubertal testes, since diols stimulated GH response to GHRH to a greater extent than testoster one [4], Differences in the effects of orchidectomy might be caused by testicular factors other than androgens. In this respect, it is well known at present that testes secrete different peptides [9] and that orchidectomy can be inter preted in terms of a blockade of steroid and peptide se cretion.…”

Section: Discussionmentioning

confidence: 99%

“…Sera were collected after centrifugation and kept frozen at -20 °C until analysis. GH levels were mea sured as previously described [3] by using materials supplied by the NIDDK and were expressed in terms of the reference prepa ration GH-RP-2. Individual responses were integrated as areas under the curve using the trapezoidal rule.…”

Section: Methodsmentioning

confidence: 99%

“…GH secretion is controlled by GHRH and somatostatin [ 1] and peripheral signals such as gonadal hormones [2,3], In adult rats, in vivo pituitary responsiveness to GHRH was shown to de crease after orchidectomy [2,3] and increased after testos terone administration [2, 4], Therefore, testicular factors other than testosterone may be involved in the modula tion of pituitary responsiveness to GHRH. This is because the in vitro GH response to GHRH remained unaltered after preincubation of dispersed cells with testosterone [2] and the increased serum testosterone levels in orchidec tomized males after testosterone administration were not accompanied by a full recovery of the in vitro pituitary response to GHRH [5].…”

Section: Introductionmentioning

confidence: 99%

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Growth Hormone-Releasing Hormone-Induced Growth Hormone Secretion in Adult Rats Orchidectomized or Injected with Ethylene Dimethane Sulphonate

Aguilar

Pinilla²,

Tena‐Sempere³

1993

Neuroendocrinology

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It is well known that GHRH-induced GH secretion decreases after orchidectomy. To verify if testicular factors other than testosterone are involved in this effect, the GHRH-induced GH secretion and testosterone plasma levels were compared in adult male rats that were either intact, treated with ethylene dimethane sulphonate (EDS) (a specific toxin for Leydig cells), orchidectomized or testosterone-treated orchidectomized. We found that testosterone plasma levels and ventral prostate weight decreased to a similar extent in orchidectomized and EDS-treated males. GHRH-induced GH secretion only decreased in orchidectomized males. We conclude that testicular factors, other than androgens, increase GHRH-induced GH secretion.

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“…In the second experiment, females were ovariectomized or sham operated under light ether anesthesia on day 23. Pituitary responsive ness was tested on days 30, 45, 60 and 90, and females in diestrus I were used as controls.…”

Section: Methodsmentioning

confidence: 99%

Ovarian Role in the Modulation of Pituitary Responsiveness to Growth Hormone-Releasing Hormone in Rats

Aguilar

Pinilla²

1991

Neuroendocrinology

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The influence of ovarian function on the pituitary responsiveness to growth hormone-releasing hormone (GHRH) was studied by measuring GH levels in serum before and after the injection of GHRH 1–29 NH2 (5 µg/kg i.v.) in female Wistar rats under sodium pentobarbital anesthesia (50 mg/kg i.p.)· In the first experiment, GHRH was administered to 90-day-old females in different phases of the estrous cycle (in the morning and afternoon of proestrus and in the morning of estrus, diestrus 1 and diestrus 2). In the second experiment, females were ovariectomized or sham-operated on day 23 and analyzed on days 30, 45, 60 and 90. Pituitary growth hormone (GH) content in females ovariectomized or sham-operated on day 23 was also analyzed at different ages. In the third experiment, females ovariectomized or sham-operated on day 83 were tested on day 90. Results showed that (a) pituitary responsiveness to GHRH changes throughout the estrous cycle is maximal in diestrus and minimal in proestrus; (b) GHRH stimulated GH secretion in intact and ovariectomized females on days 45, 60 and 90, but not on day 30; (c) the age increase of GH responsiveness to GHRH administration was slightly reduced in animals ovariectomized on day 23; (e) the age increase of pituitary GH content was similar in control and ovariectomized females; and (d) ovariectomy on day 83 reduced pituitary responsiveness to GHRH more effectively than ovariectomy on day 23. These results suggest (1) that pituitary responsiveness to GHRH changes during the estrous cycle and (2) that ovarian secretion mediates partially the age increase of the response by a mechanism not related with changes in pituitary GH content. In addition, the effects of gonadectomy on the effectiveness of GHRH depend on the time elapsed between suppression of gonadal secretion and the administration of GHRH.

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The effect of orchidectomy on rat pituitary responsiveness to GHRH depends on age

Abstract: Pituitary responsiveness to GHRH (1-29) NH2 (GHRH, 5 \g=m\g/kg iv) was analysed under sodium pentobarbital anesthesia (50 mg/kg ip), on days 30 and 90 in male rats orchidectomized or sham-operated 7 days earlier. Other groups of rats were orchidectomized or sham-

Cited by 13 publications

References 21 publications

Middle-Age Alterations in the Sexually Dimorphic Plasma Growth Hormone Profiles: Involvement of Growth Hormone-Releasing Factor and Effects on Cytochrome P450 Expression

Middle-Age Alterations in the Sexually Dimorphic Plasma Growth Hormone Profiles: Involvement of Growth Hormone-Releasing Factor and Effects on Cytochrome P450 Expression

Growth Hormone-Releasing Hormone-Induced Growth Hormone Secretion in Adult Rats Orchidectomized or Injected with Ethylene Dimethane Sulphonate

Ovarian Role in the Modulation of Pituitary Responsiveness to Growth Hormone-Releasing Hormone in Rats

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