Hedgehog Signaling and Steroidogenesis

Finco, Isabella; LaPensee, Christopher R.; Krill, Kenneth T.; Hammer, Gary D.

doi:10.1146/annurev-physiol-061214-111754

Cited by 51 publications

(36 citation statements)

References 176 publications

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“…An additional follicle-related pathway enriched in the aged multiparous ovary was the "steroid metabolic process" comprising the genes Hsd17b1, Apoa1, Apoa4, and Nr5a2. Including the Hedgehog signaling members Ihh and Dhh, known to modulate steroid biosynthesis in various organs, including the ovaries [26], there were six steroidogenic genes overexpressed in the aged multiparous relative to the aged virgin ovary.…”

Section: Follicle and Oocyte Homeostasismentioning

confidence: 99%

The Ovarian Transcriptome of Reproductively Aged Multiparous Mice: Candidate Genes for Ovarian Cancer Protection

et al. 2020

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In middle-aged women, the decline of ovarian follicle reserve below a critical threshold marks menopause, leading to hormonal, inflammatory, and metabolic changes linked to disease. The highest incidence and mortality of sporadic ovarian cancer (OC) occur at post-menopause, while OC risk is reduced by full-term pregnancies during former fertile life. Herein, we investigate how parity history modulates the ovarian transcriptome related to such declining follicle pool and systemic inflammation in reproductively-aged mice. Female C57BL/6 mice were housed under multiparous and virgin (nulliparous) breeding regimens from adulthood until estropause. The ovaries were then subjected to follicle count and transcriptional profiling, while a cytokine panel was determined in the sera. As expected, the follicle number was markedly decreased just by aging. Importantly, a significantly higher count of primordial and total follicles was observed in aged multiparous relative to aged virgin ovaries. Consistently, among the 65 genes of higher expression in aged multiparous ovaries, 27 showed a follicle count-like pattern, 21 had traceable evidence of roles in follicular/oocyte homeostasis, and 7 were transforming-growth factor beta (TGF-β)/bone morphogenetic protein (BMP) superfamily members. The remaining genes were enriched in cell chemotaxis and innate-immunity, and resembled the profiles of circulating CXCL1, CXCL2, CXCL5, CSF3, and CCL3, chemokines detected at higher levels in aged multiparous mice. We conclude that multiparity during reproductive life promotes the retention of follicle remnants while improving local (ovarian) and systemic immune-innate surveillance in aged female mice. These findings could underlie the mechanisms by which pregnancy promotes the long-term reduced OC risk observed at post-menopause.

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Section: Follicle and Oocyte Homeostasismentioning

confidence: 99%

The Ovarian Transcriptome of Reproductively Aged Multiparous Mice: Candidate Genes for Ovarian Cancer Protection

et al. 2020

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“…Shh binding relieves Ptch1-mediated inhibition of the signal transducer smoothened homolog (Smo), thereby activating downstream signaling through the zinc finger glioma-associated oncogene family (Gli) of transcription factors. The Gli family is composed of Gli1, Gli2, and Gli3, and when activated, promotes the transcription of Hh target genes (Ching and Vilain, 2009; Finco et al, 2015; Huang et al, 2010; King et al, 2009). …”

Section: Shh Signalingmentioning

confidence: 99%

Cell signaling pathways in the adrenal cortex: Links to stem/progenitor biology and neoplasia

Penny

Finco

Hammer

2017

Molecular and Cellular Endocrinology

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The adrenal cortex is a dynamic tissue responsible for the synthesis of steroid hormones, including mineralocorticoids, glucocorticoids, and androgens in humans. Advances have been made in understanding the role of adrenocortical stem/progenitor cell populations in cortex homeostasis and self-renewal. Recently, large molecular profiling studies of adrenocortical carcinoma (ACC) have given insights into proteins and signaling pathways involved in normal tissue homeostasis that become dysregulated in cancer. These data provide an impetus to examine the cellular pathways implicated in adrenocortical disease and study connections, or lack thereof, between adrenal homeostasis and tumorigenesis, with a particular focus on stem and progenitor cell pathways. In this review, we discuss evidence for stem/progenitor cells in the adrenal cortex, proteins and signaling pathways that may regulate these cells, and the role these proteins play in pathologic and neoplastic conditions. In turn, we also examine common perturbations in adrenocortical tumors (ACT) and how these proteins and pathways may be involved in adrenal homeostasis.

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“…Downstream transcriptional targets of the signaling activity include Gli1 and Ptch1 themselves, thus forming a self-regulatory feedback loop. While HH signaling plays a key role in the embryonic development of the gonads and pituitary, precisely what cell types are targeted by HH signaling at this early stage, as well as whether and how HH signaling may also regulate functions of the gonads and pituitary in adult life, remain to be defined (16,19). S100 calcium binding protein A4 (S100A4), also known as fibroblast-specific protein-1 (FSP1), is expressed in distinct stromal-interstitial cell types, such as fibroblasts, immune cells, and tumor cells (20,21).…”

Section: Introductionmentioning

confidence: 99%

S100a4-Cre–mediated deletion of Ptch1 causes hypogonadotropic hypogonadism: role of pituitary hematopoietic cells in endocrine regulation

Ren¹,

Monkkonen²,

Lewis³

et al. 2019

JCI Insight

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Hedgehog Signaling and Steroidogenesis

Cited by 51 publications

References 176 publications

The Ovarian Transcriptome of Reproductively Aged Multiparous Mice: Candidate Genes for Ovarian Cancer Protection

The Ovarian Transcriptome of Reproductively Aged Multiparous Mice: Candidate Genes for Ovarian Cancer Protection

Cell signaling pathways in the adrenal cortex: Links to stem/progenitor biology and neoplasia

S100a4-Cre–mediated deletion of Ptch1 causes hypogonadotropic hypogonadism: role of pituitary hematopoietic cells in endocrine regulation

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