Gonadotropin-Independent Regulation of Steroidogenesis in the Fetal Rat Testis1

El-Gehani, Faraj; Zhang, Fuping; Pakarinen, Pirjo; Rannikko, Antti; Huhtaniemi, Ilpo

doi:10.1095/biolreprod58.1.116

Cited by 133 publications

(98 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our findings that PACAP is required for testosterone biosynthesis in vivo are consistent with previous in vitro studies in which PACAP was shown to stimulate testosterone secretion by embryonic and adult Leydig cells (20)(21)(22)29). Nevertheless, the low testosterone concentration in PACAP Ϫ/Ϫ mice does not affect the fertility of these animals that routinely breed in our facility.…”

Section: Discussionsupporting

confidence: 92%

“…It has been suggested that steroidogenesis itself and, more specifically, the microsomal P450c17 protein (5, 6) participates in the age-induced testis degradation by generating ROS, which have been shown to negatively impact on steroidogenesis in vitro (28) and have been proposed as responsible for the age-related senescence of the Leydig cells in vivo (14). The neuropeptide PACAP has been implicated in regulation of testosterone level in cultured Leydig cells (20)(21)(22)29). It has also been shown to potentially enhance the release of LH in vivo (18).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Delayed testicular aging in pituitary adenylate cyclase-activating peptide (PACAP) null mice

Lacombe¹,

Lelièvre

Roselli

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Age-related decline in male sex hormones is a direct consequence of testicular aging. These changes in the hormonal complement cause physiological disturbances affecting the quality of life for millions of aging men. To assess the influence on testicular aging of pituitary adenylate cyclase-activating peptide (PACAP), a polypeptide that regulates testicular steroidogenesis in vitro, we compared the testicular structure and function between C57BL͞6 wild-type and PACAP ؊/؊ male mice, at 4 and 15 months of age. We show that, in 4-month-old PACAP ؊/؊ mice, steroidogenesis (evaluated by levels of testosterone, steroidogenic acute regulatory protein, 3␤-hydroxysteroid dehydrogenase, and P450c17) was impaired. However, the testicular structure of these animals was not affected. At 15 months of age, wild-type testis displayed typical signs of aging (patchy seminiferous tubules, germ cell depletion, and vacuolization), whereas testicular structure was remarkably well conserved in PACAP ؊/؊ animals. The depletion of germ cells found in wild-type animals was associated with a higher content of peroxynitrites, a marker of reactive oxygen species, and a higher number of apoptotic cells compared with PACAP ؊/؊ mice. Our results show that testicular aging is delayed in PACAP ؊/؊ animals. Because the expression levels of steroidogenic factors are low and constant over time in knockout animals, a proposed mechanism for the protection against testicular degeneration is that production of reactive oxygen species, a byproduct of steroidogenesis that induces apoptosis, is down-regulated in PACAP ؊/؊ animals.Leydig cells ͉ reactive oxygen species ͉ steroidogenesis ͉ neuropeptide ͉ andropause

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Delayed testicular aging in pituitary adenylate cyclase-activating peptide (PACAP) null mice

Lacombe¹,

Lelièvre

Roselli

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…In contrast to humans, the mouse genome does not contain a gene encoding chorionic gonadotroin. In contrast to humans, the sexual differentiation of male mice in utero can occur totally independent of LH/LHR action (El-Gehani et al, 1998;Pakarinen et al, 2002).…”

Section: Introductionmentioning

confidence: 88%

Extragonadal LH/hCG action—Not yet time to rewrite textbooks

Pakarainen¹,

Ahtiainen²,

Zhang³

et al. 2007

Molecular and Cellular Endocrinology

Self Cite

View full text Add to dashboard Cite

Please cite this article as: Pakarainen, T., Ahtiainen, P., Zhang, F.-P., Rulli, S., Poutanen, M., Huhtaniemi, I., Extragonadal LH/hCG action -not yet time to rewrite textbooks, Molecular and Cellular Endocrinology (2007), doi:10.1016/j.mce.2006 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.A c c e p t e d M a n u s c r i p t A c c e p t e d M a n u s c r i p t AbstractGonadotropins are indispensable in both sexes in the regulation of gonadal sex steroid production and gametogenesis. In addition to their well established classical actions, numerous recent publications have indicated the presence and function of luteinizing hormone/chorionic gonadotropin receptors (LH/hCG-R) in a variety of extragonadal tissues. However, the physiological significance of such effects has remained unclear. We have generated two genetically modified mouse models, one with excessive production of hCG and the other with targeted disruption of LH/hCG-R gene, and used them to address the functions of LH and hCG.Numerous gonadal and extragonadal phenotypes were found in the models with the two extremes of LH/hCG action. However, when the extragonadal effects were scrutinized in greater detail, they all appeared to arise through modification of gonadal function, either through enhanced or inhibited response to LH/hCG stimulation. Hence, further evidence is needed before the extragonadal LH/hCG-R expression can be considered functionally significant.

show abstract

“…The adult Leydig cells are completely dependent on LH support for both development and adult function; in the absence of LH few adult Leydig cells develop and circulating testosterone levels are barely detectable (O'Shaughnessy et al ., 1998; Baker & O'Shaughnessy, 2001; Lei et al ., 2001; Zhang et al ., 2001). In contrast, the foetal Leydig cells in rodents appear to function largely independently of hormonal support (El Gehani et al ., 1998; O'Shaughnessy et al ., 1998; Baker et al ., 1999; Lei et al ., 2001; Zhang et al ., 2006) although in other species LH (or hCG in humans) is required for foetal androgen production (O'Shaughnessy & Fowler, 2011). …”

Section: Leydig Cellsmentioning

confidence: 99%

Cell‐specific ablation in the testis: what have we learned?

2015

View full text Add to dashboard Cite

SummaryTesticular development and function is the culmination of a complex process of autocrine, paracrine and endocrine interactions between multiple cell types. Dissecting this has classically involved the use of systemic treatments to perturb endocrine function, or more recently, transgenic models to knockout individual genes. However, targeting genes one at a time does not capture the more wide‐ranging role of each cell type in its entirety. An often overlooked, but extremely powerful approach to elucidate cellular function is the use of cell ablation strategies, specifically removing one cellular population and examining the resultant impacts on development and function. Cell ablation studies reveal a more holistic overview of cell–cell interactions. This not only identifies important roles for the ablated cell type, which warrant further downstream study, but also, and importantly, reveals functions within the tissue that occur completely independently of the ablated cell type. To date, cell ablation studies in the testis have specifically removed germ cells, Leydig cells, macrophages and recently Sertoli cells. These studies have provided great leaps in understanding not possible via other approaches; as such, cell ablation represents an essential component in the researchers’ tool‐kit, and should be viewed as a complement to the more mainstream approaches to advancing our understanding of testis biology. In this review, we summarise the cell ablation models used in the testis, and discuss what each of these have taught us about testis development and function.

show abstract

Gonadotropin-Independent Regulation of Steroidogenesis in the Fetal Rat Testis1

Cited by 133 publications

References 48 publications

Delayed testicular aging in pituitary adenylate cyclase-activating peptide (PACAP) null mice

Delayed testicular aging in pituitary adenylate cyclase-activating peptide (PACAP) null mice

Extragonadal LH/hCG action—Not yet time to rewrite textbooks

Cell‐specific ablation in the testis: what have we learned?

Contact Info

Product

Resources

About