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Phoenix Pharmaceuticals, Inc.  |
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胰岛素样因子3[Insulin-like
Factor 3(INSL3)]: A Novel Circulating Hormone of Testis Origin
in Humans
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胰岛素样因子3（INSL3）:
一种新型灵敏的反映男性睾丸发育或功能障碍的循环激素或标记物介绍 |
胰岛素样因子3（INSL3）是松弛素－胰岛素激素家族的成员之一，它出生前后的睾丸Leydig细胞中均有表达。这种肽在胚胎发育的过程中可以促进睾丸的发育成型。几个研究机构的实验结果显示，INSL3基因或其受体基因LGR8/GREAT若发生突变，则可能会导致男性患隐睾病。有趣的是，此类突变并不会直接影响精子生成或导致睾丸的分泌功能紊乱。另外发现，除睾丸外，其他类型的组织中也有LGR8/GREAT基因的表达,在发育成熟的Leydig细胞也发现有INSL3，说明LGR8/GREAT－INSL3激素系统在成年人体内可能还担负其他生理功能。
材料与方法。在之前的一个研究报告中，我们曾经用一个新型的放免试剂盒对人INSL3进行了首次研究。我们用这个试剂盒检测了30例正常男性和10例正常女性血清中的INSL3浓度，同时也检测了各种类型睾丸病变的血清，这些病变包括：性腺激素功能低下（hypogonadotropic hypogonadism）2例、未治疗过的无睾丸病症（untreated orchiectomized men）5例、小睾丸症（Klinefelter subjects）9例、患严重男性不孕症的（severely infertile men）32例，另外还检测了10例经不同类药物作用于（如环丙氯地孕酮[ciproterone acetate]和睾丸激素[testosterone]）下丘脑-垂体-卵巢性腺轴（hyopthalamic-pituitarygonadal axis）、以及用如GnRH颉抗剂和FSH加hCG等不同方法刺激后男性血液中的INSL3含量。不同组织中LGR8的表达水平用RT-PCR的方法进行检测。
结果和结论。结果显示INSL3在成年男性血液循环中存在，它几乎全部来源于男性睾丸，血清中含量为566.3+/-163.5 pg/mL，基本与抑制素B的含量水平接近。睾丸损伤严重的，如患严重不孕症的男性血清中INSL3的含量低，INSL3水平可能是比睾丸激素水平更敏感的，能显示Legdig细胞功能状况的标志指标。血清中INSL3的浓度与LH和睾丸激素的浓度高度相关，用不同种类激素联合作用于男性下丘脑-垂体-睾丸的结果揭示INSL3的生成与LH相联系，其方式类似于LH-睾丸激素反馈通路。另外，我们发现在垂体中LRG8 mRNA表达异常，这个结果让我们得出假设：垂体－Leydig之间的联系可能通过LH和INSL3发挥作用，这个假说的确定有待进一步深入研究结果证实。
Foresta C, Bettella A, Vinanzi C, Dabrilli P, Meriggiola MC, Garolla A, Ferlin A. A novel circulating hormone of testis origin in humans. J Clin Endocrinol Metab. 2004 Dec;89(12):5952-8
正常男性青春期内血清INSL3水平的变化
以前的文献报道中提到，胰岛素样因子3（INSL3）是由睾丸Leydig细胞产生的一类激素，在成年男性体内它的分泌与这类睾丸细胞的分化状况密切相关，同时也依赖于LH的水平。但关于青春期男性INSL3的分泌与调节却知之甚少。本文中实验的目的即是想检测正常男性青春期内INSL3的含量及其与LH、FSH和睾丸激素的关系。设定的时间从2005年1月至12月，选定的实验对象是年龄范围为9.5-17.5岁的75个健康男孩，根据Tanner 分期方法（Tanner stages）均匀的分成5个小组，每组15人。按照不同的年龄和青春期发育的不同阶段分别测量了睾丸的体积、LH、FSH、睾丸激素和INSL3的浓度。结果发现，处于Tanner分期2－4期的男孩INSL3和LH水平升高，而处于2－3期的男孩FSH升高，睾丸激素水平升高则出现在3－4期的实验对象中，而处于4到5期之间的孩子则未发现有任何一种激素水平的明显变化。从结果来看，INSL3的升高似乎预示着睾丸激素将会随之升高。然而值得注意的是，处于青春4期和5期的男孩血浆中INSL3的水平只是成年男性体内INSL3水平的1/4，而FSH、LH和睾丸激素则在青春4期的时候就达到了成人的水平。INSL3与LH的密切联系则在青春期的各个阶段都明显体现出来。结论：这些关于INSL3的数据为今后的生理动力学研究提供了材料，说明青春期内随着年龄的增长，在LH的促进下Leydig细胞逐步分化，从而使血清中INSL3水平日益升高。INSL3因此可以作为Leydig细胞的分化和功能状况的指示标志物。需要提到的是，LH的持续表达似乎是青春期INSL3逐步升高至成年人水平的必要条件。INSL3在青春期发育失调的治疗中将发挥重要作用。
Ferlin A, et al. J Clin Endocrinol Metab. 2006 Jun 27; [Epub ahead of print]
睾丸生殖障碍综合症中胰岛素样因子3基因突变：
临床和功能性特征
? ??胰岛素样因子3（INSL3）在睾丸发育过程中发挥重要作用。若将Insl3基因或其富含亮氨酸重复序列的G蛋白偶连的受体（Lgr8）去除，将会导致小鼠患上隐睾病。人的INSL3突变也与隐睾病的发病相关，但并没有结论性的资料支持INSL3是一个致病诱因。在这篇文章中，我们证实了INSL3的突变与睾丸生殖障碍综合症（TDS）确实存在联系。我们从有睾丸下降不全（maldescended testes）、不育或/和睾丸癌病史的967个病例以及450个对照中对INSL3突变基因进行了筛选。我们完成了三个新型INSL3突变体的离体功能分析，发现表达LGR8的细胞中INSL3依赖性cAMP含量增加。我们还在967个病人中的其中18个身上发现了6个INSL3突变（1.9%），而在对照组中并没有突变发生。患有不同类型睾丸病变的病例（隐睾病/不育/睾丸癌）体内均可看到INSL3基因发生类似的突变。我们新发现了三种突变类型（R4H、W69R和R72K），然而对它们进行分析发现，在用LGR8受体刺激后胞内正常cAMP的水平升高。结论：我们发现男性INSL3基因突变与TDS综合症密切相关。然而，对一些突变类型的功能性分析的结果未能明确的支持INSL3突变是致病的诱因。虽然INSL3和LGR8基因突变对隐睾病的形成有促进作用的解释是合理的，我们仍需进行深入研究，发现INSL3信号通路的受阻与不育/睾丸癌之间究竟是存在着何种联系。
Ferlin A, et al. Mol Hum Reprod. 2006 Jun;12(6):401-6. Epub 2006 May 10
促性腺激素受抑制后和选择性恢复作用处理对正常成年男性胰岛素样因子3分泌的影响
背景知识：促性腺激素对由睾丸Leydig细胞分泌的激素胰岛素样因子3（INSL3）产生的作用还未完全弄清。本实验的目的即是为了确定在促性腺激素的抑制/激活或自我修复中后，INSL3水平的变化。实验设计和参与者：取了15个男性的血清，参与短期的促性腺激素激活/抑制和修复对INSL3影响的实验研究，11个男性的血清参与长期抑制后的实验研究。抑制方法：通过外源的睾丸激素和孕酮抑制促性腺激素的分泌，而外源的促性腺激素则能帮助生殖腺的自我修复和激素分泌。结果分析：所示结果为血清INSL3与其他生殖激素间的关系。结果：血清中INSL3对促性腺激素并不特别敏感，在短期和长期抑制实验中，INSL3随着促性腺激素被抑制而急剧下降（为基础水平的6％－13.5%;P<0.05）。在短期实验组中，用人绒毛膜促性腺激素（hCG）处理后4天里被抑制的血清INSL3得到部分恢复（从基础水平的7.5%恢复至38.3%; P<0.05），其恢复升高的幅度与血清中pro-alphaC的升高呈现相关（r=0.82; P<0.01）。而FSH则不能刺激被抑制的INSL3恢复。在长期实验组中，当血清中LH完全恢复至正常的前体下，血清中睾丸激素恢复（基础水平的80％）的程度明显好于INSL3（基础水平的38.9%; P<0.01）。结论：在正常男性体内INSL3对促性腺激素的刺激作用不敏感，但若促性腺激素匮乏，其含量急剧下降。其分泌收到抑制后，用hCG处理4天后INSL3可相应得到恢复。而在长期抑制的情况下，INSL3则不能象睾丸激素那样恢复到基础水平，说明Leydig细胞发生异常后，INSL3比睾丸激素更容易受影响。
Bay K, et al. J Clin Endocrinol Metab. 2006 Mar;91(3):1108-11. Epub 2006 Jan 4.
核受体在Leydig细胞INSL3基因转录中的作用
胰岛素样因子3(INSL3)是由睾丸Leydig细胞在整个生命周期内稳定分泌产生的一种激素.在真核生物的生命历程中,它对雄性睾丸发育成熟至关重要,是保持成熟男性精子细胞成活的重要因子.尽管INSL3对男性性别分化和男性功能的作用很重要,但关于调控其表达的分子机制却知之甚少.到目前为止,仅知道核受体SF-1作为转录因子,可以调节小鼠Leydig细胞中Insl3启动子的活性.为了更深入的了解调控INSL3转录表达的机制,我们分离了人INSL3启动子序列,并设计实验试图找到Leydig细胞中核受体SF-1、LRH-1和Nur77对INSL3启动子活性的影响.通过细胞转染实验我们发现,三种核受体都能激活人INSL3启动子的活性,而Nur77的激活效应最明显,这是之前未报道过的新的可刺激INSL3表达的转录调节因子.因此我们得出:INSL3启动子是孤核受体Nur77的新靶位点.
Tremblay JJ, Robert NM. Ann N Y Acad Sci. 2005 Dec;1061:183-9
人良性前列腺肥大增生及前列腺癌中的INSL3
众所周知,松弛素H1和H2是由人前列腺分泌的,但关于INSL3肽激素在前列腺中的表达情况和生理功能方面的资料却泛陈可乏.在本文中,我们检测了良性前列腺肥大(BPH)、前列腺上皮瘤(PIN) 和前列腺癌患者的病变组织中的INSL3表达情况.在前列腺上皮细胞的基底部我们发现有大量INSL3的表达,而mRNA和免疫反应的结果显示,在分泌性上皮细胞和空腔平滑肌细胞中INSL3的阳性较弱.研究还发现,前列腺上皮细胞可转录编码INSL3的受体LGR8,说明在人的前列腺中存在一个自分泌/旁分泌型的INSL3/LGR8配体-受体系统.三种不同的人前列腺癌细胞系中INSL3和LGR8基因活性有所区别.在LNCaP细胞中没有发现INSL3的表达,而对雄性激素不敏感的PC-3细胞和前列腺间质细胞hPCP则都能转录表达INSL3和LGR8.DU-145细胞系不表达LGR8,却可转录INSL3 mRNA,除此以外,发现其存在一种INSL3的接合体,这种物质之前常在甲状腺癌细胞中检测到.我们用重组INSL3孵育PC-3细胞后,发现胞内的cAMP水平升高,说明PC-3细胞含有功能性的LGR8受体,不过INSL3的处理并没有导致PC-3癌细胞增殖周期和代谢活性发生改变,而是明显增强了肿瘤细胞的浸润性,并引发ErbB受体和EGF的转录活性下调.用全反式维甲酸(All-trans-retinoic acid)处理PC-3细胞发现,LGR8基因活性上调,并呈时间和剂量依赖性,但对INSL3基因的活性则没有影响.结论:我们在若干种人胰岛素癌细胞中证实,存在一INSL3-LGR8配体-受体的功能调控系统.
Klonisch T, et al. Int J Oncol. 2005 Aug;27(2):307-15 |
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Introduction.
Insulin-like factor 3 (INSL3) is a member of
the relaxin-insulin family, and it is expressed
in pre- and postnatal Leydig cells of the testis.
This peptide affects testicular descent during
embryonic development. Studies from our group
and others showed a clear association between
mutations in INSL3 gene or its receptor LGR8/GREAT
and cryptorchidism also in humans. Interestingly,
these mutations seem not to directly affect spermatogenesis
or endocrine function of the testis. The expression
of LGR8/GREAT in different tissues and the production
of INSL3 also by adult-type Leydig cells, suggest
additional roles of this hormonal system in adulthood.
Materials
and Methods. In this preliminary report,
we performed the first analysis in humans of
INSL3 using a novel radioimmunoassay kit to
measure INSL3 concentrations in serum of normal
men (n=30) and women (n=10), and with different
testicular pathologies, including, hypogonadotropic
hypogonadism. (n=2), subjects with untreated
orchiectomized men (n=5), Klinefelter subjects
(n=9), severely infertile men (32), and in
men treated with different kinds of hormonal
regimen of the hyopthalamic-pituitarygonadal
axis (such as ciproterone acetate and testosterone,
as male contraception program (n=10), and different
stimulation tests (such as with GnRH analogue
and FSH plus hCG). Analysis of the expression
of LGR8 in different tissues was performed
by RT-PCR.
Results
and Conclusions. The results show that
INSL3 is circulating in adult men, and it is
of almost exclusive testis origin. Serum concentrations
are 566.3+/-163.5 pg/mL.and therefore at the
same range of inhibin B. Subjects with severe
testicular damage, such as men with severe
infertility, produce low amount of INSL3, and
the concentrations of this hormone seem to
reflect the functional status of the Leydig
cells. In particular, INSL3 concentrations
may even be a more sensitive marker of Leydig
cell function than testosterone itself. INSL3
serum concentrations are positively correlated
with LH and with testosterone concentrations.
Analysis of men treated with different combinations
of hormones of the hypothalamic-pituitary-testis
axis suggests that the production of INSL3
is related LH, in a manner similar to that
of the LH-testosterone axis. We found a specific
expression of LRG8 mRNA at the pituitary level
and this finding supports the hypothesis of
a possible pituitary-Leydig axis involving
LH and INSL3, even if further studies are in
progress to confirm these results.
Dr.
Ferlin has declared that he does not have a financial
relationship with any manufacturer/s of any commercial
product/s.
Foresta C, Bettella A, Vinanzi C, Dabrilli P, Meriggiola
MC, Garolla A, Ferlin A. A novel circulating hormone
of testis origin in humans. J Clin Endocrinol Metab.
2004 Dec;89(12):5952-8 |
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| Changes in serum Insulin-like factor 3
(INSL3) during normal male puberty |
Context Insulin-like factor 3 (INSL3) is produced
by the Leydig cells and in adults its secretion is
dependent on the state of differentiation of these
cells, which, in turn, is dependent on LH. However,
the secretion and regulation of INSL3 during puberty
is unknown. Objective To evaluate INSL3 concentrations
during normal male puberty and its relation to LH,
FSH and testosterone. Design Cross-sectional study
conducted from January to December 2005. Setting
Academic clinics Patients 75 healthy male subjects
aged 9.5-17.5 yr, homogeneously distributed into
five pubertal groups of 15 according to Tanner stages.
Interventions None Main outcome measures Mean testicular
volume and LH, FSH, testosterone and INSL3 concentrations
in relation to age and pubertal stage. Results We
observed an increase of INSL3 and LH levels from
Tanner stage 2 to 4, and an increase of FSH from
stage 2 to 3. Testosterone levels increased from
stage 3 to 4. No differences were seen for all measured
hormones between stage 4 and 5. The increase in INSL3
seems therefore to anticipate the increase in testosterone.
However, INSL3 plasma concentrations at pubertal
stages 4 and 5 are about one fourth of adult levels,
whereas FSH, LH and testosterone reached adult levels
by stage 4. Positive significant correlations were
found between INSL3 and LH for all pubertal stages.
Conclusions This study provides information on the
physiological dynamics of INSL3 showing that the
serum concentrations of this hormone increased progressively
throughout puberty, under the differentiating action
of LH on Leydig cells. INSL3 is therefore confirmed
to represent a marker of Leydig cell differentiation
and function. However, a prolonged exposition to
LH seems to be necessary to reach INSL3 concentrations
of adults. A possible use of INSL3 in puberty disorders
is promising.
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| Ferlin A, et al. J Clin Endocrinol Metab. 2006
Jun 27; [Epub ahead of print] |
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| Insulin-like factor 3 gene mutations in
testicular dysgenesis syndrome: clinical and functional
characterization |
Insulin-like factor 3 (INSL3) plays a crucial role
in testicular descent. Genetic ablation of Insl3
or its G protein-coupled receptor, leucine-rich repeat-containing
G-protein-coupled receptor (Lgr8), causes cryptorchidism
in mice. Mutation analyses of INSL3 in humans showed
an association with cryptorchidism but led to non-conclusive
data about a causative role. In this study, we explored
the hypothesis that mutations in INSL3 may be associated
with the signs of testicular dysgenesis syndrome
(TDS). We screened for mutations in INSL3 gene in
967 subjects with a history of maldescended testes
and/or infertility and/or testicular cancer and in
450 controls. Furthermore, we carried out in vitro
functional analysis of three novel mutations by analysis
of INSL3-dependent cAMP increase in cells expressing
LGR8. We found six INSL3 mutations in 18 of 967 patients
(1.9%) and no mutations in controls. Prevalence of
mutations was similar in the different groups of
patients (cryptorchidism and/or infertility and/testicular
cancer). Three mutations were novel findings (R4H,
W69R, and R72K); however, their analysis showed normal
cAMP increase after the activation of LGR8 receptor.
In conclusion, we found a significant association
of INSL3 gene mutations in men presenting one or
more signs of TDS syndrome. However, a causative
role for some of these mutations is not clearly supported
by functional analyses. Although a role for mutations
of INSL3 and LGR8 genes in cryptorchidism is reasonable,
additional studies are needed to establish an association
between the disruption of INSL3 pathway and higher
risk of infertility or testicular cancer.
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| Ferlin A, et al. Mol Hum Reprod. 2006 Jun;12(6):401-6.
Epub 2006 May 10 |
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| The effects of gonadotropin suppression
and selective replacement on insulin-like factor
3 secretion in normal adult men |
CONTEXT: Gonadotropic regulation
of the testicular Leydig cell hormone insulin-like
factor 3 (INSL3) is incompletely characterized.
OBJECTIVE: The objective of this study was to assess
the effects of gonadotropin suppression and induced
or spontaneous recovery on serum INSL3. DESIGN
AND PARTICIPANTS: Serum samples from 15 men enrolled
in a short-term study of gonadotropin stimulation,
suppression, and recovery and 11 men in a long-term
study of gonadotropin suppression and spontaneous
recovery were analyzed for INSL3. Intervention:
Gonadotropins were suppressed by exogenous testosterone
and progestin. Recovery was spontaneous or induced
with exogenous gonadotropins. OUTCOME MEASURE:
The outcome measure was serum INSL3 in relation
to other reproductive hormones. RESULTS: Serum INSL3
was not acutely sensitive to gonadotropins. In both
studies, INSL3 declined markedly with gonadotropin
suppression (6-13.5% of baseline; P < 0.05). In
the short-term study, human chorionic gonadotropin
partially restored suppressed serum INSL3 within
4 d of administration (from 7.5 to 38.3% baseline;
P < 0.05); the increase correlated with the corresponding
increase in serum pro-alphaC (r = 0.82; P < 0.01).
FSH did not stimulate the suppressed INSL3. In the
long-term study, serum testosterone recovered significantly
better (80% baseline) compared with serum INSL3 (38.9%
baseline; P < 0.01) in the presence of fully recovered
serum LH. CONCLUSIONS: INSL3 is not sensitive to
gonadotropin stimulation in normal men, but declines
markedly in response to gonadotropin deprivation.
After suppression, INSL3 was responsive to hCG 4
d after administration. After long-term suppression,
INSL3 did not recover to the same degree as testosterone,
suggesting that INSL3 is more sensitive to Leydig
cell impairment than testosterone.
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| Bay K, et al. J Clin Endocrinol Metab. 2006 Mar;91(3):1108-11.
Epub 2006 Jan 4. |
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| Role of nuclear receptors in INSL3 gene
transcription in Leydig cells |
Insulin-like 3 (INSL3) is a hormone produced by
testicular Leydig cells throughout life. During embryonic
life it regulates an essential step of testicular
descent, whereas in adults it acts as a male germ
cell survival factor. Despite the importance of INSL3
for male sex differentiation and function, very little
is known regarding the molecular mechanisms that
regulate its expression. So far, the nuclear receptor
SF-1 is the only transcription factor known to regulate
the mouse Insl3 promoter in Leydig cells. In order
to further our understanding of the transcriptional
regulation of INSL3 expression, we have isolated
the human INSL3 promoter and tested the effects of
the nuclear receptors SF-1, LRH-1, and Nur77 on its
activity in Leydig cells. In transfections assays,
all three nuclear receptors activated the human INSL3
promoter but especially Nur77, which acted through
a novel regulatory element. Thus, the human INSL3
promoter constitutes a novel target for the orphan
nuclear receptor Nur77.
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| Tremblay JJ, Robert NM. Ann N Y Acad Sci. 2005
Dec;1061:183-9 |
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| INSL3 in the benign hyperplastic and neoplastic
human prostate gland |
The human prostate gland is
a well known source of H1 and H2 relaxin but information
is lacking on the expression and potential role
of the INSL3 peptide hormone within the prostate
gland. In the present study we have investigated
the expression of human INSL3 in patients with benign
prostate hyperplasia (BPH), prostate intraepithelial
neoplasia (PIN) and prostate carcinoma tissues.
Of the prostate epithelial cells, strongest INSL3
expression was detected in the basal epithelial
cell compartment. Weaker INSL3 mRNA expression and
immunoreactive INSL3 production were observed in
secretory epithelial cells and in interstitial smooth
muscle cells. Prostate epithelial cells were also
a source for transcripts encoding the INSL3 receptor
LGR8 suggesting the presence of an autocrine/paracrine
INSL3-LGR8 ligand-receptor system within the human
prostate. Three human prostate carcinoma cell lines
displayed differential gene activity for INSL3 and
LGR8. While LNCaP was devoid of INSL3, the androgen-insensitive
PC-3 and the stromal prostate cell line hPCP co-expressed
INSL3 and LGR8 transcripts. In addition to expressing
INSL3 mRNA, the LGR8-negative DU-145 also expressed
an INSL3 splice form formerly demonstrated in thyroid
carcinoma cells. When incubated with recombinant
INSL3, PC-3 cells showed significantly increased
intracellular cAMP levels indicating functional
LGR8 receptors. INSL3 did not alter the proliferative
or metabolic activity of PC-3 carcinoma cells. Instead,
PC-3 responded to INSL3 with significantly enhanced
tumor cell motility and a transcriptional down-regulation
of ErbB receptors and EGF. All-trans-retinoic acid
was demonstrated in PC-3 to up-regulate LGR8 gene
activity in a dose- and time-dependent manner while
having no effect on INSL3 gene activity. In conclusion,
we have identified a functional INSL3-LGR8 ligand-receptor
system in human prostate carcinoma cells. |
Klonisch T, et al. Int J Oncol. 2005 Aug;27(2):307-15
|
|
| Standard curve (F; triplicate measurements) and
parallelism analysis (f) of pooled diluted serum samples.
Foresta C, et al. J Clin Endocrinol Metab. 2004 Dec;89(12):5952-8 |
|
| Individual determinations of INSL3
concentrations in the different groups of subjects.
Continuous and dashed lines indicate the mean value
and the 95% confidence intervals, respectively. The
mean SD are as follows: normal adult men, 562.3
155.4 pg/ml (range, 310.1–908.5 pg/ml; 95%
confidence interval, 514.2–610.1 pg/ml); normal
adult women in the follicular phase, 99.5 21.7 pg/ml
(range, 69.0–130.4 pg/ml; 95% confidence interval,
86.1–112.9 pg/ml); untreated orchidectomized
men, 69.526.3 pg/ml (range, 52.5–108.0 pg/ml;
95% confidence interval, 27.7–111.3 pg/ml);
untreated Klinefelter’s syndrome, 157.5 77.1
pg/ml (range, 28.2–237.5 pg/ml; 95% confidence
interval, 98.2–216.7 pg/ml); severely infertile
men, 289.0 69.0 pg/ml (range, 142.0–425.0
pg/ml; 95% confidence interval, 265.1–312.9
pg/ml); and hypogonadotropic hypogonadism, 63.2
6.7 pg/ml (range, 58.5–68.0 pg/ml; 95% confidence
interval, 2.9–123.6 pg/ml). °, P 0.05
vs. normal adult men; *, P 0.001 vs. normal adult
men; #,P0.05 vs. Klinefelter’s syndrome, untreated
orchidectomized men, hypogonadotropic hypogonadism,
and normal adult women. Foresta C, et al. J Clin Endocrinol
Metab. 2004 Dec;89(12):5952-8 |
|
|
|
Positive correlations between INSL3 and LH (r
0.6; P 0.001; A) and between INSL3 and testosterone
(r 0.7; P 0.001; B), and absence of relation between
INSL3 and FSH (r 0.1; P 0.42; C) in normal males.
Foresta C, et al. J Clin Endocrinol Metab. 2004 Dec;89(12):5952-8 |
|
|
| A, Individual determinations of INSL3 concentrations
in 10 normal men at baseline and after 16 wk of therapy
with CPA (50 mg twice a day, orally) plus TE (100
mg/wk, im). Mean concentrations SD are as follows:
693.3 131.8 pg/ml (range, 519.5–908.5; 95%
confidence interval, 599.0–787.6 pg/ml) at baseline
and 139.8 64.9 pg/ml (range, 68.0–281.5 pg/ml;
95% confidence interval, 93.4–186.2 pg/ml) after
therapy (P 0.001). B, Individual determinations
of INSL3 concentrations in two infertile men at baseline,
30 d after administration of the GnRH analog leuprolide
(3.75 mg, im), and during the following 2-month therapy
with r-hFSH (100 IU every day, im) and hCG (2000 IU
twice per week, im). Mean concentrations SD are
as follows: 328.6 125.8 pg/ml at baseline, 52.7
23.1 pg/ml after the GnRH analog, 307.5 123.7
pg/ml after 1 month of therapy with gonadotropins,
and 339.5 120.9 pg/ml after 2 months of therapy
with gonadotropins.Foresta C, et al. J Clin Endocrinol
Metab. 2004 Dec;89(12):5952-8 |
|
Individual determinations of INSL3 concentrations
in six men withHHat baseline and after 1 month of
therapy withhCG(2000 IU twice per week, im). Mean
concentrations SD are as follows: 55.2 7.9 pg/ml
(range, 46.8–68.0; 95% confidence interval,
48.9– 61.5 pg/ml) at baseline and 111.4 7.6
pg/ml (range, 100.0–115.1; 95% confidence interval,
105.3–117.5 pg/ml) after therapy (P 0.05).
|
Median
and 95% confidence intervals of the median of
measurements of age, INSL3, testosterone, LH,
FSH, and mean testicular volume at each stage
of puberty. Values for adults (15) are reported
for comparison |
|
|
Correlation of INSL3 with LH in all
subjects (n: 75). The regression line (solid line)
and 95% confidence intervals (dotted lines) are indicated.
r: 0.92; 95% confidence intervals: 0.87-0.95;
P<0.001. |
|
|
Individual serum concentrations of
INSL3 and mean testicular
volume in 75 healthy boys as a function of age.
|
|
|
|
|
Scatter diagram
of individual serum concentrations of LH, FSH,
testosterone, and INSL3 at each stage of puberty
(15 subjects per stage). The median is indicated
by solid lines. Significance is indicated when
the median is statistically different from the
median of the previous stage of puberty. *P<0.001;
**P<0.005; §P<0.05.
Values for adults (15) are reported for comparison. |
|
|
|
|
| |
Catalog No. |
Product Name |
Quantity |
$US/ Euro |
|
035-27 |
INSL
3 (RLF)(Human) |
100 礸 |
350 |
|
RK-035-27 |
INSL
3 (RLF)(Human), RIA Kit |
1 kit |
550 |
|
EK-035-27 |
INSL
3 (RLF)(Human), EIA Kit |
1 kit |
450 |
|
T-035-27 |
INSL
3 (RLF)(Human), Iodine 125 Labeled Tracer |
10 礐i |
650 |
|
H-035-27 |
INSL
3 (RLF)(Human), Antiserum for Immunohistochemistry |
100 祃 |
450 |
|
G-035-27 |
INSL
3 (RLF)(Human), Purified IgG Antibody |
200 礸 |
450 |
|
FC5-G-035-27 |
INSL
3 (RLF)(Human), Purified IgG, Cy5 Labeled |
100 祃 |
525 |
|
FC3-G-035-27 |
INSL
3 (RLF)(Human), Purified IgG, Cy3 Labeled |
100 祃 |
525 |
|
FG-G-035-27 |
INSL
3 (RLF)(Human), Purified IgG, FAM Labeled |
100
祃 |
500 |
|
FRP-G-035-27 |
INSL
3 (RLF)(Human), R-PE Labeled Purified IgG |
100 祃 |
550 |
|
B-G-035-27 |
INSL
3 (RLF)(Human), Purified IgG, Biotin Labeled |
100
祃 |
500 |
|
B-035-27 |
INSL
3 (RLF)(Human), Monobiotinylated, Biotin Labeled |
20 礸 |
350 |
|
|
|
| |
|
