Changes in Serum Testosterone Levels Following Acute LH Treatment in Immature and Mature Rats1

Wh, Moger; Dt, Armstrong

doi:10.1095/biolreprod11.1.1

Cited by 46 publications

(14 citation statements)

References 6 publications

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“…Typically the GPCR regulates acute changes and the steroid receptor leads to more long-term regulation of gene expression. Similarly, because testosterone levels can change acutely in response to a variety of stimuli (66,67), GPRC6A may provide a mechanism to respond to short-term variations in circulating androgen levels and may work in concert with the AR in more chronic responses. Regardless, the new biological insight from these studies is that GPRC6A-mediated non-genomic responses and AR-dependent genomic responses can have coordinated functional effects in androgen responsive tissues.…”

Section: Discussionmentioning

confidence: 99%

GPRC6A Mediates the Non-genomic Effects of Steroids

Parrill

Quarles

2010

Journal of Biological Chemistry

169

143

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The identity of the putative G-protein coupled receptor (GPCR) that mediates the non-genomic effects of androgens is unknown. We present in vitro and in vivo evidence that the orphan GPRC6A receptor, a widely expressed calcium and amino acid sensing GPCR, transduces the non-genomic effects of testosterone and other steroids. Overexpression of GPRC6A imparts the ability of extracellular testosterone to illicit a rapid, non-genomic signaling response in HEK-293 cells lacking the androgen receptor. Conversely, testosterone-stimulated rapid signaling and phosphorylation of ERK is attenuated in bone marrow stromal cells derived from GPRC6A Androgens are important regulators of reproductive physiology and anabolic biological activities in multiple tissues (1). In addition, androgens also play a role in the pathogenesis of prostate cancer, including disease severity, progression, and metastasis (2, 3). The classical genomic actions of androgens are mediated through the androgen receptor (AR), 3 a member of the nuclear receptor superfamily of transcription factors (4 -6). Androgen binding to AR and translocation of the steroid-receptor complex to the nucleus regulates steroid response elements in promoters to modulate gene expression over a period of hours (7). Androgens and selective androgen receptor modulators are being explored as therapy for agerelated conditions, such as osteopenia and sarcopenia (8). In addition, androgens illicit rapid (occurring in minutes) nongenomic effects that may also have important biological effects in many tissues (5, 9 -11). The molecular mechanisms underlying these non-genomic actions are poorly understood. Several mechanisms have been proposed, including translocation of the steroid receptors to the cell surface membrane (12-14), nonspecific effects of steroids on the fluidity of lipids in the plasma membrane, direct allosteric modification of ligand-gated ion channels (5), and activation of G-protein coupled receptors (GPCRs) (9, 15, 16), including a putative pertussis toxin-sensitive GPCR (17-21). Identification of the putative GPCR that transduces the non-genomic effects of androgens may add significantly to our understanding of androgen biology that is relevant to normal human development and disease as well as the health risks of excessive pharmacological doses of anabolic steroids used in body building.GPRC6A is a pertussis toxin-sensitive member of the C family of GPCRs that senses amino acids, extracellular calcium, and osteocalcin (22-24). GPRC6A may function as an anabolic receptor coordinating the responses of multiple tissues to changes in nutrients and other factors (25). In this regard, ablation of this orphan G-protein coupled receptor leads to testicular feminization in male mice, suggesting that GPRC6A may also modulate sex steroid end organ responses (25).In the present study, we examined the role of GPRC6A in mediating the non-genomic effects of androgens on cell function in vitro and in vivo. We found that GPRC6A mediates the rapid signaling response to testostero...

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Section: Discussionmentioning

confidence: 99%

GPRC6A Mediates the Non-genomic Effects of Steroids

Parrill

Quarles

2010

Journal of Biological Chemistry

169

143

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“…In the rat an increase in the secretion of testosterone after identical doses of HCG can be demonstrated with the approach of puberty (Moger & Armstrong, 1974;Ode11 et al, 1974). This could be explained in part by a progressive decline of testicular 5a-reductase activity (Strickland et al, 1970), and in part by an increase of the number of receptor sites in the testis for gonadotrophins (Frowein & Engel, 1975).…”

Section: (B) Increase Of Hypothalamic-pituitary-gonadal Sensitivity Tmentioning

confidence: 99%

Hypothalamic‐pituitary‐gonadal Relationships in Man From Birth to Puberty

Forest

Peretti

Bertrand

1976

Clinical Endocrinology

134

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Gonadal function depends upon activities at various levels. Thus there is: (a) a central level (extra-hypothalamic, hypothalamic, and anterior pituitary); (b) an intermediate level (gonadal and plasma), and (c) a peripheral level consisting of the target organs to which the hormonal message is directed. These determine both the expression of gonadal function (physical, physiological, or psychological) and the feedback regulation of the secretion of gonadotrophins.(a) Central level (i) Extra-hypothalamic centres. The production of LH releasing hormone (LHRH) is affected in the rat, and probably in primates as well, by extra-hypothalamic stimuli coming, in particular, from the amygdala and the hippocampus. Adrenergic regulation exists at this level, noradrenaline having a stimulatory and dopamine an inhibitory effect (Bliss et al., 1972).(ii) Hypothalamic centres. These are localized in particular in the pre-optic area. Immunochemical techniques have demonstrated that LHRH is secreted by neurones of the arcuate nucleus, and released into the capillary plexus proximal to the hypophyseal portal system at the level of the median eminence, thereby reaching the anterior pituitary (Barry & Dubois, 1974;Setalo et al., 1975).(iii) Gonadotrophin secreting cells of the anterior pituitary. These synthesize and secrete the gonadotrophins, LH and FSH, under the influence of LHRH (Schally et al., 1972). The pituitary gonadotrophins stimulate the synthesis and the secretion of the gonadal

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“…Administration of exogenous lutehizing hormone ( L H ) to the intact male rat has been shown to increase testosterone secretion in a dose dependent fashion, the response to LH stimulation being much greater in the adult than in the immature animal (1,2).…”

Section: Selin and Mogermentioning

confidence: 99%

The Effect of FSH on LH Induced Testosterone Secretion in the Immature Hypophysectomized Male Rat

Selin

Moger

1977

Endocrine Research Communications

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The effect of gonadotropin pretreatment of hypophysectomized male rats on LH stimulated serum testosterone concentrations was studied. A 5 day pretreatment period began 2 days after hypophysectomy at 21 or 24 days of age. On the day following the pretreatment period the animals received an intraperitoneal injection of saline or LH 60 min before blood collection. Animals pretreated with NIH-FSH-B1, or with doses of LH approximating the amount present in the NIH-FSH, had increased testosterone concentrations after LH stimulation compared to similarly stimulated saline pretreated animals. Pretreatment with more highly purified FSH Ex 199C at a lower dose than the minimum effective dose of NIH-FSH was also effective. There was no synergistic or additive effect when FSH Ex 199C and LH pretreatments were combined. FSH Ex 199C is more potent and contains appreciably less LH contamination than NIH-FSH-B1. The results obtained using FSH Ex 199C indicate that FSH, independent of LH contamination, can increase testes response to LH stimulation.

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Changes in Serum Testosterone Levels Following Acute LH Treatment in Immature and Mature Rats1

Cited by 46 publications

References 6 publications

GPRC6A Mediates the Non-genomic Effects of Steroids

GPRC6A Mediates the Non-genomic Effects of Steroids

Hypothalamic‐pituitary‐gonadal Relationships in Man From Birth to Puberty

The Effect of FSH on LH Induced Testosterone Secretion in the Immature Hypophysectomized Male Rat

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