Regulation of Gonadal and Somatotropic Axis by Chronic Intraventricular Infusion of Insulin-Like Growth Factor 1 Antibody at the Initiation of Puberty in Male Rats

Pazos, Fernando; Sánchez‐Franco, Franco; Balsa, José Antonio; López-Fernández, Judith; Escalada, Javier; Cacicedo, Lucinda

doi:10.1159/000054443

Cited by 37 publications

(22 citation statements)

References 47 publications

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“…Prepubertal rats receiving intracerebroventricular IGF-1 experienced an earlier pubertal onset, as indicated by vaginal opening, than rats given saline (7). In agreement with this finding, male rats given intracerebroventricular IGF-1 antibody experienced puberty, as indicated by serum testosterone level and testicular weight, significantly later than rats given vehicle (8). Female mice with deletion of the growth hormone receptor experience delayed puberty, as indicated by vaginal opening, that is advanced by IGF-1 administration (9).…”

Section: Introductionsupporting

confidence: 74%

Divergent roles of growth factors in the GnRH regulation of puberty in mice

et al. 2010

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Pubertal onset, initiated by pulsatile gonadotropin-releasing hormone (GnRH), only occurs in a favorable, anabolic hormonal milieu. Anabolic factors that may signal nutritional status to the hypothalamus include the growth factors insulin and IGF-1. It is unclear which hypothalamic neuronal subpopulation these factors affect to ultimately regulate GnRH neuron function in puberty and reproduction. We examined the direct role of the GnRH neuron in growth factor regulation of reproduction using the Cre/lox system. Mice with the IR or IGF-1R deleted specifically in GnRH neurons were generated. Male and female mice with the IR deleted in GnRH neurons displayed normal pubertal timing and fertility, but male and female mice with the IGF-1R deleted in GnRH neurons experienced delayed pubertal development with normal fertility. With IGF-1 administration, puberty was advanced in control females, but not in females with the IGF-1R deleted in GnRH neurons, in control males, or in knockout males. These mice exhibited developmental differences in GnRH neuronal morphology but normal number and distribution of neurons. These studies define the role of IGF-1R signaling in the coordination of somatic development with reproductive maturation and provide insight into the mechanisms regulating pubertal timing in anabolic states.

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Section: Introductionsupporting

confidence: 74%

Divergent roles of growth factors in the GnRH regulation of puberty in mice

et al. 2010

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“…Zhen et al (33) showed that IGF-I increased the expression of gonadotropin-releasing hormone in vitro. Although the intracerebroventricular administration of IGF-I antibodies resulted in delayed puberty in male rats (34), intraventricular injections of IGF-I advanced puberty in female rats (35). In contrast, a recent study of 76 prepubertal girls showed an inverse correlation between IGF-I and 25(OH)D (36).…”

Section: Discussionmentioning

confidence: 91%

Vitamin D deficiency and age at menarche: a prospective study

Villamor¹,

Marín²,

Mora‐Plazas³

et al. 2011

The American Journal of Clinical Nutrition

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Background: Early menarche is a risk factor for cardiometabolic disease and cancer. Latitude, which influences sun exposure, is inversely related to age at menarche. This association might be related to vitamin D, but to our knowledge it has not been investigated in prospective epidemiologic studies. Objective: We studied the association between vitamin D status and the occurrence of menarche in a prospective study in girls from Bogota, Colombia.concentrations in a random sample of 242 girls (mean 6 SD age: 8.8 6 1.6 y) and followed them for a median of 30 mo. Girls were asked periodically about the occurrence and date of menarche. Baseline 25(OH)D concentrations were categorized as ,50 nmol/L (deficient), 50 and ,75 nmol/L, or 75 nmol/L (sufficient). The incidence of menarche was compared between groups by using time-to-event analyses. Results: A total of 57% of girls in the vitamin D-deficient group reached menarche during follow-up compared with 23% of girls in the vitamin D-sufficient group (P-trend = 0.0004). The estimated mean (6SE) ages at menarche in the same groups were 11.8 6 0.2 y and 12.6 6 0.2 y, respectively (P = 0.0009). After adjustment for baseline age and BMI-for-age z score in a Cox proportional hazards model, the probability of menarche was twice as high in vitamin D-deficient girls than in girls who were vitamin D-sufficient (HR: 2.05; 95% CI: 1.03, 4.07; P = 0.04). Similar results were obtained in girls aged 9 y at baseline (HR: 2.39; 95% CI: 1.14, 5.00; P = 0.02).

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“…In several species, including man, monkey, rat and mouse [1, 8, 13, 21], female puberty is associated with a GH-induced increased expression of IGF-1 in the liver on the morning of the first proestrus, resulting in increased levels of serum IGF-1, which peak during proestrus afternoon accompanied by increases in serum LH, FSH, and E 2 [4, 6, 9]. Both peripherally and centrally derived IGF-1 can accelerate the onset of puberty in juvenile rats, via a stimulation of the GnRH release [4].…”

Section: Discussionmentioning

confidence: 99%

“…Around puberty the plasma level of IGF-1 increases due to an elevated hepatic IGF-1 gene expression and production, induced by the also increasing GH level [4,5,6]. In prepubertal rats IGF-1 of peripheral origin directly acts on GnRH neurons and affects GnRH synthesis and release [1, 4,6,7,8]. Absence of IGF-1 delayed normal maturation in male and female mice [1, 9], whereas ventricular infusion (i.c.v.)…”

Section: Introductionmentioning

confidence: 99%

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Central Application of IGF-1 Postpones Time of Vaginal Opening in Normally Fed, but Not in Food-Restricted Rats

Zeinoaldini

Swarts²,

Heijning³

2006

Horm Res Paediatr

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Background/Aims: Central but also peripheral IGF-1 is suggested to play a role in the initiation of puberty as it directly affects GnRH synthesis and release. A possible intermediate in the effects of IGF-1 on puberty might be the adiposity-signaling hormone leptin, whose plasma levels are decreased in food-restricted (FR) rats. Methods: IGF-1 was chronically centrally infused in 23-day-old prepubertal female rats which were either normally fed or 30% FR, and the effects on time of vaginal opening (VO) and plasma leptin levels were monitored. Results: FR treatment postponed time of VO and decreased plasma leptin levels. In normally fed rats centrally infused with IGF-1, time of VO was found to be postponed to the same extent as FR treatment did. The IGF-1 infusion did not affect plasma leptin levels in normally fed animals but increased leptin levels in the FR group compared to controls. Daily food intake was equal between all groups but body weight course was lower in FR rats. IGF-1 treatment did not significantly affect food intake or body weight course. Conclusion: FR treatment delays the moment of vaginal opening to the same extent as observed in normally fed rats that were centrally infused with IGF-1.

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Regulation of Gonadal and Somatotropic Axis by Chronic Intraventricular Infusion of Insulin-Like Growth Factor 1 Antibody at the Initiation of Puberty in Male Rats

Cited by 37 publications

References 47 publications

Divergent roles of growth factors in the GnRH regulation of puberty in mice

Divergent roles of growth factors in the GnRH regulation of puberty in mice

Vitamin D deficiency and age at menarche: a prospective study

Central Application of IGF-1 Postpones Time of Vaginal Opening in Normally Fed, but Not in Food-Restricted Rats

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