Pituitary Hyperplasia, Hormonal Changes and Prolactinoma Development in Males Exposed to Estrogens—An Insight From Translational Studies

Šošić‐Jurjević, Branka; Ajdžanović, Vladimir; Miljić, Dragana; Trifunović, Svetlana; Filipović, Branko; Stankovic, S.; Bolevich, Sergey; Jakovljević, Vladimir; Milošević, Verica

doi:10.3390/ijms21062024

Cited by 10 publications

(8 citation statements)

References 142 publications

(220 reference statements)

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“…It is well known that estrogen stimulates the pituitary stem/progenitor cell differentiation in the direction of a lactotrophic cell line. 60 In addition, it has been reported that estrogen regulates the SC of the human reproductive system, which induces SC proliferation and participates in the regulation of SC populations in a paracrine manner. 61 In summary, we have analyzed the expression of SC/TSC markers at different stages of hyperplastic/adenomatous pituitary development.…”

Section: Discussionmentioning

confidence: 99%

Changes of stem cell niche during experimental pituitary tumor development

Guido

Sosa

Pérez

et al. 2021

J Neuroendocrinology

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To investigate the putative stem cell/tumor stem cell (SC/TSC) niche contribution to hyperplasic/adenomatous pituitary lesions, we analyzed variation in the pituitary stem cell population during the development of experimental pituitary tumors. Pituitary tumors were induced in female F344 rats with estradiol benzoate for 5, 10, 20 and 30 days. Cells positive for GFRa2, Sox2, Sox9, Nestin, CD133 and CD44 were identified in the marginal zone and in the adenoparenchyma in both control and 30D groups, with predominant adenoparenchyma localization of GRFa2 and SOX9 found in tumoral pituitaries. GFRa2, Nestin, CD133 and CD44 were upregulated at the initial stages of tumor growth, whereas Sox9 significantly decreased at 5D, with Sox2 remaining invariable during the hyperplasic/adenomatous development. In addition, isolated pituispheres from normal and tumoral pituitary glands enriched in SC/TSC were characterized. Pituispheres from the 30D glands were positive for the above-mentioned markers and showed a significant increase in the proliferation. In conclusion, our data revealed pituitary SC pool fluctuations during hyperplastic/adenomatous development, with differential localization of the SC/TSC niche in this process. These findings may help to provide a better understanding of these cell populations, which is crucial for achieving advancements in the field of pituitary tumor biology.

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Section: Discussionmentioning

confidence: 99%

Changes of stem cell niche during experimental pituitary tumor development

Guido

Sosa

Pérez

et al. 2021

J Neuroendocrinology

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“…In prolactinomas, tumor growth related to oral estrogen therapy has already been re-ported, since these types of tumors present a significant ER expression [ 88 , 89 ]. An important role might also be played, especially in males, by the intra-tumoral activity of aromatase, which locally transforms testosterone into estradiol [ 90 ].…”

Section: Clinical Use Of Estrogens And/or Serms In Patients With Acro...mentioning

confidence: 99%

Role of Estrogen and Estrogen Receptor in GH-Secreting Adenomas

Voltan

Mazzeo

Regazzo

et al. 2023

IJMS

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Acromegaly is a rare disease with several systemic complications that may lead to increased overall morbidity and mortality. Despite several available treatments, ranging from transsphenoidal resection of GH-producing adenomas to different medical therapies, complete hormonal control is not achieved in some cases. Some decades ago, estrogens were first used to treat acromegaly, resulting in a significant decrease in IGF1 levels. However, due to the consequent side effects of the high dose utilized, this treatment was later abandoned. The evidence that estrogens are able to blunt GH activity also derives from the evidence that women with GH deficiency taking oral estro-progestins pills need higher doses of GH replacement therapy. In recent years, the role of estrogens and Selective Estrogens Receptor Modulators (SERMs) in acromegaly treatment has been re-evaluated, especially considering poor control of the disease under first- and second-line medical treatment. In this review, we analyze the state of the art concerning the impact of estrogen and SERMs on the GH/IGF1 axis, focusing on molecular pathways and the possible implications for acromegaly treatment.

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“…Dopamine inhibits proliferation of lactotroph cells, prolactin synthesis and release, acting via the D2R expressed in lactotroph cells [20]. Estrogen hormones may contribute to pathogenesis of prolactinomas, as these tumors grow faster during pregnancy and develop in transsexual men under estrogen treatment [23,24]. Estradiol and estrogens in general decrease the effects of dopamine agonists, induce prolactin gene transcription and indirectly lower dopamine synthesis from the hypothalamus [6,20,25].…”

Section: Molecular Pathogenesis Of Prolactinomas Important To Design Future Treatments Estrogenmentioning

confidence: 99%

Treatment Strategies for Dopamine Agonist-Resistant and Aggressive Prolactinomas: A Comprehensive Analysis of the Literature

et al. 2021

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Despite most of the prolactinomas can be treated with endocrine therapy and/or surgery, a significant percentage of these tumors can be resistant to endocrine treatments and/or recur with prominent invasion into the surrounding anatomical structures. Hence, clinical, pathological, and molecular definitions of aggressive prolactinomas are important to guide for classical and novel treatment modalities. In this review, we aimed to define molecular endocrinological features of dopamine agonist-resistant and aggressive prolactinomas for designing future multimodality treatments. Besides surgery, temozolomide chemotherapy and radiotherapy, peptide receptor radionuclide therapy, estrogen pathway modulators, progesterone antagonists or agonists, mTOR/akt inhibitors, pasireotide, gefitinib/lapatinib, everolimus, and metformin are tested in preclinical models, anecdotal cases, and in small case series. Moreover, chorionic gonadotropin, gonadotropin releasing hormone, TGFβ and PRDM2 may seem like possible future targets for managing aggressive prolactinomas. Lastly, we discussed our management of a unique prolactinoma case by asking which tumors’ proliferative index (Ki67) increased from 5–6% to 26% in two subsequent surgeries performed in a 2-year period, exerted massive invasive growth, and secreted huge levels of prolactin leading up to levels of 1 605 671 ng/dl in blood.

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Pituitary Hyperplasia, Hormonal Changes and Prolactinoma Development in Males Exposed to Estrogens—An Insight From Translational Studies

Cited by 10 publications

References 142 publications

Changes of stem cell niche during experimental pituitary tumor development

Changes of stem cell niche during experimental pituitary tumor development

Role of Estrogen and Estrogen Receptor in GH-Secreting Adenomas

Treatment Strategies for Dopamine Agonist-Resistant and Aggressive Prolactinomas: A Comprehensive Analysis of the Literature

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