Induction of Endogenous Insulin-Like Growth Factor-I Secretion Alters the Hypothalamic-Pituitary-Testicular Function in Growth Hormone-Deficient Adult Dwarf Mice1
Abstract
To evaluate the influence of growth hormone (GH) on hypothalamic-pituitary-testicular function, GH-deficient adult male Ames dwarf mice were treated (s.c.) twice daily for 8 days with either vehicle or bovine GH (25 μg/injection/mouse). Normal male siblings treated with vehicle served as controls. Two in vivo experiments were conducted. In experiment 1, on Day 8, mice were treated (i.p.) with either saline or LHRH (1 ng/g b.w.) in saline. Fifteen minutes later, blood was obtained via heart puncture to assess plasma insulin-like growth factor-I (IGF-I), LH, and testosterone (T) levels by RIAs. In experiment 2, on Day 7, mice were bilaterally castrated and received injections of either oil or T propionate (1 μg/g b.w.) in oil. Eighteen to twenty hours later, blood was obtained as in experiment 1, and plasma IGF-I and LH levels were determined. In addition to these in vivo experiments, testicular androstenedione and T responses to hCG stimulation in vitro were evaluated. Administration of GH to dwarf mice increased (p < 0.001) plasma IGF-I levels, whereas IGF-I was not detectable in control dwarf mice. Plasma IGF-I concentrations were higher in normal mice than in treated dwarf mice. Basal LH levels were lower (p < 0.025) in dwarf mice than those in normal mice. In dwarf mice, GH treatment increased (p < 0.001) plasma LH levels. The effect of LHRH on LH secretion was increased (p < 0.001) in dwarf mice pretreated with GH, but this LH response was lower than in normal siblings that received vehicle only. The castration-induced increase in plasma LH levels was attenuated (p < 0.05) in GH-deficient mice. However, GH treatment to these mice resulted in an increase (p < 0.001) in plasma LH levels. The suppressive effect of T propionate was attenuated (p < 0.001) in dwarf mice previously treated with GH. Although basal plasma T levels were similar in both normal and dwarf mice, plasma T response to the increase in plasma LH levels by LHRH treatment was decreased (p < 0.001) in vehicle-treated dwarf mice. Plasma T levels were similar in dwarf mice treated with GH and in vehicle-treated normal mice. Pretreatment of dwarf mice with GH resulted in increased production of androstenedione and T by the isolated testis treated with hCG. However, this response was higher (p < 0.001) in incubations containing testis obtained from normal mice. These results indicate that the hypothalamic-pituitary-testicular function is impaired in dwarf mice with hereditary GH deficiency and that induction of IGF-I secretion by GH treatment partially corrects these abnormalities. Therefore, it is conceivable that the derangement of neuroendocrine-testicular function in GH-deficient mice is due to lack of IGF-I secretion. Since these dwarf mice are also prolactin-deficient and exhibit hypothyroid symptoms, it is possible that GH, prolactin, and thyroid hormones may be required to establish normal hypothalamic, pituitary, and testicular functions in adult Ames dwarf mice.
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Induction of IGF-1 secretion by GH treatment can partially recover the impaired HPG axis.
“The induction of IGF-1 secretion by GH treatment can partially recover the impaired HPG axes (12).”
From Growth Hormone Is Beneficial for Induction of Spermatogenesis in Adult Patients With Congenital Combined Pituitary Hormone Deficiency (2022) · cites this paper as [12]
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- Authors
- Chandrashekar, V., & Bartke, A.
- Affiliations
- Southern Illinois University Carbondale (US)
- Corresponding author
- Chandrashekar, Varadaraj
- Venue
- Biology of Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 1993-03-01
- Volume
- 48
- Issue
- 3
- Pages
- 544-551
- ISSN
- 0006-3363 (ISSN-L)
- 1529-7268
- OpenAlex
- W2142848812
- Cited by
- 108
- References
- 35
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 5 · 2016: 4 · 2015: 1 · 2014: 3 · 2013: 2 · 2012: 3
- FWCI
- 3.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biology of Reproduction (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hd020033-12)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-20033)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Keywords
- growth hormone deficiency, Ames dwarf mice, insulin-like growth factor I, hypothalamic-pituitary-testicular axis, luteinizing hormone secretion, testosterone, testosterone propionate, castration, testicular testosterone, growth hormone replacement therapy, male reproduction, hypogonadism
- MeSH terms
- Animals, Dwarfism, Feedback, Hypothalamo-Hypophyseal System, Insulin-Like Growth Factor I, Luteinizing Hormone, Gonadotropin-Releasing Hormone, Male, Mice, Mutant Strains, Orchiectomy, Growth Hormone, Testis, Testosterone, Mice, In Vitro Techniques
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