Abstract

BackgroundIt is well known that somatotrophic/insulin signaling affects lifespan in experimental animals, and one of the signs of aging is progressive gonadal dysfunction.MethodsTo study the effects of insulin-like growth factor-1 (IGF-1) plasma level on ovaries, we analyzed ovaries isolated from 2-year-old growth hormone receptor knockout (GHR-KO) Laron dwarf mice, with low circulating plasma levels of IGF-1, and 6-month-old bovine growth hormone transgenic (bGHTg) mice, with high circulating plasma levels of IGF-1. The ages of the Laron dwarf mutants employed in our studies were selected based on their overall survival (up to ~ 4 years for Laron dwarf mice and ~ 1 year for bGHTg mice).ResultsMorphological analysis of the ovaries of mice that reached ~50% of their maximal life span revealed a lower biological age for the ovaries isolated from 2-year-old Laron dwarf mice than their normal-lifespan wild type littermates. By contrast, the ovarian morphology of increased in size 6 month old bGHTg mice was generally normal.ConclusionOvaries isolated from 2-year-old Laron dwarf mice exhibit a lower biological age compared with ovaries from normal WT littermates at the same age. At the same time, no morphological features of accelerated aging were found in 0.5-year-old bGHTg mice compared with ovaries from normal the same age-matched WT littermates.

Highlights

  • Senescence is a physiological process related to changes in many tissues and organs, including dysfunction of the endocrine system, and among the first changes observed are a decrease in growth hormone (GH) and sex GH circulating in plasma stimulates liver secretion of somatomedin-C, known as insulin-like growth factor -I (IGF-1), which affects the function of several organs, including the gonads

  • Ovarian morphology in 2-year-old laron dwarf mice and normal age-matched wild type (WT) littermate controls The morphological structure of ovaries from normal 2year-old WT mice exhibited a blurred border between cortex and medulla

  • The surface of the ovaries was covered by a simple cuboidal epithelium, and the ovarian cortex lacked the ovarian follicles observed in the ovaries of younger mice at reproductive age

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Summary

Introduction

Senescence is a physiological process related to changes in many tissues and organs, including dysfunction of the endocrine system, and among the first changes observed are a decrease in growth hormone (GH) and sex GH circulating in plasma stimulates liver secretion of somatomedin-C, known as insulin-like growth factor -I (IGF-1), which affects the function of several organs, including the gonads. GH/IGF-I signaling affects (i) release of gonadotropin-releasing hormone (GnRH) and gonadotropins, (ii) expression of receptors for gonadotropins in ovarian granulosa cells and in Leydig cells in testes, and (iii) development of mammary glands. GH controls early phases of follicle development and stimulates formation of secondary follicles and the development of granulosa and theca cells. Silva et al [9] suggest that GH is the survival factor for primary follicles and regulates differentiation of granulosa cells. It is well known that somatotrophic/insulin signaling affects lifespan in experimental animals, and one of the signs of aging is progressive gonadal dysfunction

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