Actions and interactions of alcohol and insulin-like growth factor-1 on female pubertal development - PubMed (original) (raw)

Review

Actions and interactions of alcohol and insulin-like growth factor-1 on female pubertal development

W Les Dees et al. Alcohol Clin Exp Res. 2009 Nov.

Abstract

Alcohol (ALC) is a drug that is capable of disrupting reproductive function in adolescent humans, as well as immature rhesus monkeys and rats. Critical to determining the mechanism(s) of the effects of ALC on the pubertal process is to have a better understanding of the important events involved in the initiation of puberty. For years it has been hypothesized that there may be metabolic signals capable of linking somatic growth to the activation of the reproductive system at the time of puberty. In recent years it has been shown that insulin-like growth factor-1 (IGF-1) is one such signal that plays an early role in the pubertal process. In this review, we will describe the actions and interactions of ALC and IGF-1 on molecular and physiological processes associated with pubertal development.

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Figures

Fig. 1

Effects of ALC on the serum levels of puberty-related hormones and on menstrual patterns in developing rhesus monkeys. Blood samples were drawn from the saphenous vein twice daily (0830 hours am and 2030 hours pm) and their averages for 5 consecutive days determined each monkey’s respective hormone level over the sampling period. Each data point represents the mean (±SEM) 5-day hormone levels from 5 control and 5 ALC-treated rhesus monkeys at each designated month. (A) GH levels were suppressed in the ALC-treated monkeys at 28 and 32 months of age. (B) LH levels were suppressed from 24 to 32 months. (C) E2 levels increased markedly between 28 and 32 months of age in the control monkeys, an action that did not occur in the ALC-treated monkeys, hence causing them to be suppressed at these time points. (D) The interval between menstruations for the ALC-treated monkeys was almost twice that of the controls. Solid and open bars represent the means (±SEM) of control and ALC-treated animals, respectively. *p < 0.05; **p < 0.01; ***p < 0.001. N = 4 to 5 animals per group. Panels A–C were assessed by ANOVA, followed by Student–Neuman–Keul’s post-hoc test. Panel D was assessed by Student’s _t_-test.

Fig. 2

Serum IGF-1, LH, and E2 levels during pubertal development in the female rat. (A) The serum levels of IGF-1 increased during early proestrus (EP), peaked at late proestrus (LP), and remained elevated over the juvenile (JUV) levels through first estrus (E). (B and C) The serum levels of LH and E2 were also elevated during late proestrus. (D) Daily administration of IGF-1 advanced the time of vaginal opening. The respective bars represent the mean (±SEM) of an N of 25 to 40 animals per group in A–C and 6 to 7 per group in D. *p < 0.05 and **p < 0.01, by ANOVA with post-hoc testing using the Student–Newman–Keuls multiple range test; ***p < 0.001, by _t_-test.

Fig. 3

Effects of chronic ALC administration on IGF-1 gene expression in the liver and on the serum levels of IGF-1 and LH. (A) Densitometric quantitation of bands generated by RNase protection showing that liver IGF-1a mRNA expression was markedly suppressed in the ALC-treated animals. Similar results were also observed for IGF-1b expression (not shown). (B and C) ALC exposure also concomitantly suppressed serum levels of both IGF-1 and LH. The respective bars represent the mean (±SEM) of an N of 7 to 8 animals per group in A, and 26 to 36 per group in B and C. **p < 0.001.

Fig. 4

Schematic drawing showing the actions and interactions of alcohol (ALC) and insulin-like growth factor-1 (IGF-1) related to growth and puberty. ALC not only acts peripherally to suppress IGF-1 synthesis in the liver, and hence circulating levels of the peptide available to the hypothalamus, but can also act centrally to block important IGF-1 actions. The cumulative effect of altered hypothalamic IGF-1 signaling is suppressed growth hormone releasing hormone (GHRH) and luteinizing hormone releasing hormone (LHRH) secretion at a critical time of development. Ultimately, these reductions lead to suppressed growth hormone (GH), luteinizing hormone (LH), and estradiol (E2) secretion, resulting in altered growth and pubertal development. Preoptic area (POA); anteroventral periventricular nucleus (AVPV); arcuate nucleus (ARC); median eminence (ME); medial basal hypothalamus (MBH); anterior pituitary (AP); posterior pituitary (PP); somatotroph (SOM); gonadotroph (GON); hepatocyte (HC).

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Actions and interactions of alcohol and insulin-like growth factor-1 on female pubertal development - PubMed (original) (raw)