In vivo and in vitro Regulation of Pituitary Transcription Factor-1 (Pit-1) by Changes in the Hormone Environment

González‐Parra, S.; Chowen, Julie A.; García‐Segura, Luis M.; Argente, Jesús

doi:10.1159/000126930

Cited by 40 publications

(28 citation statements)

References 48 publications

(85 reference statements)

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“…Castration of adult male rats results in a significant decrease in GH mRNA levels and this decline is inhibited by testosterone replacement (22). However, in primary cultures, we found no effect of sex steroids on GH mRNA levels (22), which is in contrast to one report showing a slight increase in response to 17b-oestradiol (23).…”

Section: Sex Steroid Effects On the Anterior Pituitarycontrasting

confidence: 99%

The regulation of GH secretion by sex steroids

Chowen

Frago

Argente

2004

European Journal of Endocrinology

108

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Gonadal sex steroids modulate GH synthesis and secretion with effects on both the hypothalamus and anterior pituitary. In the post-pubertal animal, androgens and oestrogens modulate hypothalamic somatostatin (SS) and GHRH synthesis respectively. These effects may be direct as SS neurons express the androgen receptor and many GHRH neurons are oestrogen receptor positive. The neonatal steroid environment modulates the number of GHRH neurons in the adult hypothalamus, as well as their responsivity to post-pubertal steroids. Furthermore, both neonatal and post-pubertal steroids modulate hypothalamic synaptic organisation affecting the number of synaptic inputs and the morphology of glial cells. This in turn has important effects on the ability of the hypothalamus to drive the secretory pulsatility of anterior pituitary hormone release. At the level of the somatotroph, androgens and oestrogens have been reported to stimulate, inhibit or have no effect on GH synthesis. In primary cultures, we found no effect of either androgens or oestrogens on GH mRNA levels. However, the sex steroid environment significantly modified the response of somatotrophs to SS. Furthermore, males have more somatotrophs compared with female rats and this partially depends on the neonatal sex steroid environment. In conclusion, sex steroids have both organisational and activational effects on the GH axis. These effects range from modulating the number of hypothalamic neurons controlling GH secretion, their responsiveness to later steroids, and the synaptic connectivity and neuropeptide production, to modulation of somatotroph numbers in the anterior pituitary and their responsiveness to inputs controlling GH synthesis and secretion.European Journal of Endocrinology 151 U95-U100

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Section: Sex Steroid Effects On the Anterior Pituitarycontrasting

confidence: 99%

The regulation of GH secretion by sex steroids

Chowen

Frago

Argente

2004

European Journal of Endocrinology

108

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“…Sex steroids modulate the IGF -GH axis at the level of the hypothalamus (33,44,45), pituitary (46,47) and target tissues (19,42,43). In addition, the response of some cells to GH or IGF-I depends on the presence of sex steroids and vice versa and sex steroid actions on the GH -IGF-I axis are also age-dependent (48).…”

Section: Discussionmentioning

confidence: 99%

Interaction between malnutrition and ovarian hormones on the systemic IGF-I axis

Goya

García‐Segura²,

Ramos³

et al. 2002

European Journal of Endocrinology

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Objective: In malnutrition both the GH -IGF and reproductive axes are greatly affected. Because the actions of IGF and sex steroids are inter-dependent in many tissues, we have examined how ovariectomy modulates the response of the systemic IGF system to undernutrition. Design and methods: Peripubertal (30 days of age) female rats were either sham operated or ovariectomized. Five days later half of each group was submitted to a protein-caloric restriction diet. All rats were killed at 60 days of age. Results: Growth was decreased in all rats submitted to calorie restriction and this was consistent with a decrease in circulating IGF-I concentrations and liver IGF-I mRNA expression. While in normally fed rats ovariectomy had no significant effect on serum IGF-I concentrations, ovariectomized and underfed rats had significantly higher levels than intact underfed rats. In undernourished rats, serum IGF-binding proteins (IGFBP)-1, -2 and -3 concentrations were significantly reduced and this was not modified by ovariectomy. In contrast, liver mRNA concentrations of IGFBP-1 and -2 were increased and IGFBP-3 unchanged in intact undernourished animals, suggesting that undernutrition could be affecting the proteolysis of these binding proteins, and this response was significantly modulated by ovariectomy. Conclusion: These results indicate that the presence of circulating ovarian hormones significantly affects the response of the IGF system to undernutrition.

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“…In vitro transcription of digoxigenin riboprobes was carried out according to the manufacturer's instructions (Roche, Barcelona, Spain). The riboprobes, in situ hybridisation methodology and pertinent controls have been described previously [6].…”

Section: Methodsmentioning

confidence: 99%

The number of lactotrophs is reduced in the anterior pituitary of streptozotocin-induced diabetic rats

et al. 2003

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Aims/hypothesis. Prolactin secretion is often reduced in insulin dependent diabetes mellitus, but little is known about the mechanism involved. Since changes in the hormonal environment modulate cell proliferation, death and cellular makeup of the anterior pituitary, we have analysed whether the number of lactotrophs is reduced in diabetic rats. Methods. Streptozotocin induced diabetic rats were maintained hyperglycaemic for 2 months. Pituitary prolactin, growth hormone, Bcl-2, Bax and PCNA concentrations were analysed by western blot analysis. In situ hybridisation was used for quantification of prolactin and growth hormone mRNA containing cells. Cell death was detected by TUNEL labelling, alone and in combination with immunocytochemistry for prolactin or growth hormone.Results. Diabetic rats had fewer lactotrophs (p<0.01). This was coincident with a decrease in overall protein and prolactin content. An increase in pituitary cell death was found and some of the TUNEL labelling colocalised with prolactin immunostaining. No change in the concentration of Bcl-2 or Bax, proteins implicated in apoptosis, was detected. PCNA content was higher in the pituitaries of diabetic rats, suggesting increased proliferation. Conclusion/interpretation. Anterior pituitary cell turnover is affected in poorly controlled diabetes mellitus. A decrease in the number of lactotrophs, as a result of increased cell death, could underlie, at least in part, the reduction in prolactin secretion observed in diabetic animals. [Diabetologia (2003) 46:634-638] Keywords Lactotroph, prolactin, somatotroph, growth hormone, pituitary, cell turnover, apoptosis, Bcl-2, Bax, proliferation. but not pulse frequency [1]. Furthermore, the secretory activity of individual lactotrophs is not impaired in diabetic rats [3], suggesting diminished stimulatory input to these cells. However, a decrease in the number of lactotrophs could also explain a reduction in PRL output, with no loss in synthetic capacity of individual lactotrophs. The anterior pituitary undergoes cellular turnover during adulthood and this is affected by changes in the hormonal environment [4]. Hence, the cellular makeup of the anterior pituitary could be affected in diabetes mellitus. We have analysed whether the number of lactotrophs is modulated in poorly controlled diabetic rats and the possible mechanisms involved in this process.In poorly controlled diabetic patients or laboratory animals, circulating prolactin (PRL) concentrations and PRL responses to secretory stimuli are often suppressed [1,2,3]. This results from a decrease in pulse amplitude, peak area and interpulse concentrations,

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In vivo and in vitro Regulation of Pituitary Transcription Factor-1 (Pit-1) by Changes in the Hormone Environment

Cited by 40 publications

References 48 publications

The regulation of GH secretion by sex steroids

The regulation of GH secretion by sex steroids

Interaction between malnutrition and ovarian hormones on the systemic IGF-I axis

The number of lactotrophs is reduced in the anterior pituitary of streptozotocin-induced diabetic rats

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