Mammary gland-specific regulation of GNRH and GNRH-receptor gene expression is likely part of a local autoregulatory system in female vizcachas (Rodentia: Chinchillidae)

Corso, María Clara; Cortasa, Santiago Andrés; Schmidt, Alejandro Raúl; Proietto, Sofía; Inserra, Pablo Ignacio Felipe; Fernández, Marina Olga; Giorgio, Noelia Di; Lux‐Lantos, Victoria; Vitullo, Alfredo Daniel; Dorfman, Verónica Berta; Halperín, Julia

doi:10.1016/j.ygcen.2020.113518

Cited by 4 publications

(16 citation statements)

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“…Significantly, the maximum levels of hypothalamic expression of those factors were detected at mid-pregnancy, coincidently with LH surge (Charif et al, 2017;Dorfman et al, 2013;Inserra et al, 2017. In addition, a significant increase of PRL has been detected in pituitary glands of vizcachas from mid-pregnancy onward, with its maximum at term pregnancy (Corso et al, 2020;Proietto et al, 2018). This denotes PRL and PRLR as essential players in the modulation of HPO axis of this species.…”

Section: Introductionmentioning

confidence: 66%

“…Absence of both ovulatory stigmata in the ovaries and milk in the mammary glands was verified at the time of sacrifice. In order to study the effect of hyperprolactinemia, hyperprolactinemic status was experimentally induced by Sulpiride Aires, Argentina) diluted in HCl 0.1 N (pH 7.4) (Corso et al, 2020).…”

Section: Pharmacologic Experimental Approachmentioning

confidence: 99%

“…The 4day-treated group did not show significant changes in the transcription levels of pituitary PRL, while the 10-day-treated group showed severe behavior alterations (lack of feeding and lethargy) at the 10th day of treatment and animals were immediately sacrificed. The 7-day-treated group showed significant increment in the pituitary PRL mRNA and in the mammary gland α-lactalbumin (LALBA) mRNA (being LALBA a PRL target gene in mammary gland) without behavioral alterations (Corso et al, 2020). Considering these results, the 7-day treatment was chosen for the study.…”

Section: Pharmacologic Experimental Approachmentioning

confidence: 99%

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Hypothalamic GnRH expression and pulsatility depends on a balance of prolactin receptors in the plains vizcacha, Lagostomus maximus

Cortasa

Schmidt

Proietto

et al. 2023

J of Comparative Neurology

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In mammals, gestation is considered a physiological hyperprolactinemia status. Prolactin (PRL) is one of the modulators of gonadotropin‐releasing hormone (GnRH) neurons function. The South American plains vizcacha (Lagostomus maximus) is a unique model to study the regulation of hypothalamic GnRH neurons by direct and indirect steroid‐dependent pathways. The aim was to characterize the hypothalamic expression of endocrine markers in vizcacha during gestation as well as their response to experimental induced hyperprolactinemia. The possible involvement of PRL regulatory pathways on GnRH in the context of hypothalamic and pituitary reactivation in mid‐gestating vizcachas was discussed. Using two in vivo approaches, we determined changes in the hypothalamic expression and distribution of prolactin receptor (PRLR), tyrosine hydroxylase (TH), and dopamine type 2 receptor. A significant increment in the number of tuberoinfundibular dopaminergic (TIDA) neurons was determined in the arcuate nucleus from early to term pregnancy. On the other hand, at preoptic area, the number of both TH+PRLR+ and GnRH+PRLR+ double‐labeled neurons significantly decreased at mid‐pregnancy probably allowing the recovery of GnRH expression indicating that both types of neurons may represent the key points of PRL indirect and direct pathways modulating GnRH. Moreover, in a model of induced hyperprolactinemic vizcachas, the inhibitory effect of PRL on GnRH at both expression and delivery levels were confirmed. These results suggest the concomitant participation of both PRL regulatory pathways on GnRH modulation and pinpoint the key role of PRL on GnRH expression enabling the recovery of the hypothalamic activity during the gestation in this species.

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Section: Introductionmentioning

confidence: 66%

Section: Pharmacologic Experimental Approachmentioning

confidence: 99%

Section: Pharmacologic Experimental Approachmentioning

confidence: 99%

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Hypothalamic GnRH expression and pulsatility depends on a balance of prolactin receptors in the plains vizcacha, Lagostomus maximus

Cortasa

Schmidt

Proietto

et al. 2023

J of Comparative Neurology

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“…Animals were grouped according to their reproductive status as the following: pregnant before HPO reactivation (BP), pregnant after HPO reactivation (AP), term-pregnant (TP) and nonpregnant (NP) (Table 1). To establish the different groups, the time of capture was planned according to the natural reproductive cycle of the vizcachas previously described by Llanos and Crespo [33] and based on our own field expertise [34][35][36]. Pregnant vizcachas were captured during the breeding season that lasts from April to August.…”

Section: Animalsmentioning

confidence: 99%

Achieving full-term pregnancy in the vizcacha relies on a reboot of luteal steroidogenesis in mid-gestation (Lagostomus maximus, Rodentia)

et al. 2022

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Reactivation of the hypothalamic-pituitary-ovarian (HPO) axis triggered by the decline in serum progesterone in mid-gestation is an uncommon trait that distinguishes the vizcacha from most mammals. Accessory corpora lutea (aCL) developed upon this event have been proposed as guarantors of the restoration of the progesterone levels necessary to mantain gestation. Therefore, the steroidogenic input of primary CL (pCL) vs aCL was evaluated before and after HPO axis-reactivation (BP and AP respectively) and in term pregnancy (TP). Nonpregnant-ovulated females (NP) were considered as the pCL-starting point group. In BP, the ovaries mainly showed pCL, whose LH receptor (LHR), StAR, 3β-HSD, 20α-HSD, and VEGF immunoexpressions were similar or lower than those of NP. In AP, luteal reactivity increased significantly compared to the previous stages, and the pool of aCL developed in this stage represented 20% of the ovarian structures, equaling the percentage of pCL. Both pCL and aCL luteal cells shared similar histological features consistent with secretory activity. Although pCL and aCL showed equivalent labeling intensity for the luteotropic markers, pCL were significantly larger than aCL. Towards TP, both showed structural disorganization and loss of secretory characteristics. No significant DNA fragmentation was detected in luteal cells throughout gestation. Our findings indicate that the LH surge derived from HPO axis-reactivation targets the pCL and boost luteal steroidogenesis and thus progesterone production. Because there are many LHR-expressing antral follicles in BP, they also respond to the LH stimuli and luteinize without extruding the oocyte. These aCL certainly contribute but it is the steroidogenic restart of the pCL that is the main force that restores progesterone levels, ensuring that gestation is carried to term. Most importantly, the results of this work propose luteal steroidogenesis reboot as a key event in the modulation of vizcacha pregnancy and depict yet another distinctive aspect of its reproductive endocrinology.

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“…Tumor cells activate the GnRHR pathway through autocrine and paracrine mechanisms to regulate biological behavior. [4][5][6][7][8][9] The POEMS study found that the addition of gonadotropin-releasing hormone (GnRH) analogs to postoperative chemotherapy for ER/PR-negative breast cancer significantly improved disease-free survival (DFS) and overall survival (OS) (P ¼ 0.09 and 0.06, respectively). 10 In neoadjuvant chemotherapy, it was also observed that GnRH analogs improved the complete tumor remission rate of ER/PR-negative breast cancers.…”

Section: Introductionmentioning

confidence: 99%

Gonadotropin-releasing hormone receptor inhibits triple-negative breast cancer proliferation and metastasis

Chen¹,

2022

J Int Med Res

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Background Gonadotropin-releasing hormone receptor (GnRHR) is expressed in several malignant tumors and inhibits the proliferation and metastasis of cancer cells, but its role in triple-negative breast cancers (TNBCs) is unclear. This study investigated the biological effects of GnRHR and their influence on TNBC prognosis. Methods The GSE21653 database was used to obtain information about GnRHR expression and clinicopathological factors in patients with TNBC. GnRHR was activated in cultured MDA-MB-231 and MDA-MB-468 cells by leuprolide acetate and antagonized by elagolix sodium. Cell proliferation was assessed by the cell counting kit-8 and colony formation assays. Cell metastasis was detected by the wound healing assay and Transwell assay. Apoptosis and the cell cycle were investigated by flow cytometry. GnRHR protein expression was determined by western blotting. Results GnRHR mRNA expression was significantly higher in patients with TNBC than in hormone receptor+/human epidermal growth factor receptor (HER)2– and HER2+ patients with breast cancer. Patients with high GnRHR expression had significantly better disease-free survival than those with lower expression. Activated GnRHR significantly inhibited cell proliferation and metastasis, increased apoptosis, and enhanced GnRHR protein expression levels. Conclusion GnRHR inhibits TNBC proliferation and metastasis, suggesting it could be targeted for TNBC treatment.

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Mammary gland-specific regulation of GNRH and GNRH-receptor gene expression is likely part of a local autoregulatory system in female vizcachas (Rodentia: Chinchillidae)

Cited by 4 publications

References 62 publications

Hypothalamic GnRH expression and pulsatility depends on a balance of prolactin receptors in the plains vizcacha, Lagostomus maximus

Hypothalamic GnRH expression and pulsatility depends on a balance of prolactin receptors in the plains vizcacha, Lagostomus maximus

Achieving full-term pregnancy in the vizcacha relies on a reboot of luteal steroidogenesis in mid-gestation (Lagostomus maximus, Rodentia)

Gonadotropin-releasing hormone receptor inhibits triple-negative breast cancer proliferation and metastasis

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