Adrenarche and skeletal maturation during luteinizing hormone releasing hormone analogue suppression of gonadarche.

Wierman, Margaret E.; Beardsworth, David; Crawford, John D.; Crigler, John F.; Mansfield, M. Joan; Bode, Hans H.; Boepple, Paul A.; Kushner, David C.; Crowley, William F.

doi:10.1172/jci112265

Cited by 81 publications

(45 citation statements)

References 32 publications

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“…However, several reports suggest that DHEAS promotes bone density. For example, DHEAS levels were correlated with skeletal maturation [37]. Additionally, DHEAS is positively correlated to BMD and declines with age [38][39][40][41].…”

Section: Discussionmentioning

confidence: 95%

Carnitine and Dehydroepiandrosterone Sulfate Induce Protein Synthesis in Porcine Primary Osteoblast-Like Cells

et al. 1999

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Abstract. Age-related bone loss eventually leads to osteopenia in men and women. The etiology of age-related bone loss is currently unknown; however, decreased osteoblast activity contributes to this phenomenon. In turn, osteoblast proliferation and function is dependent on energy production, thus the loss of energy production that occurs with age may account for the deficient osteoblast activity. Carnitine and dehydroepiandrosterone-sulfate (DHEAS), both of which decline with age, promote energy production through fatty acid metabolism. Thus, we hypothesized that carnitine and DHEAS would increase osteoblast activity in vitro. Accordingly, we measured the effect of carnitine and DHEAS on palmitic acid oxidation as a measure of energy production, and alkaline phosphatase (ALP) activity and collagen type I (COL) as indices of osteoblast function in primary porcine osteoblast-like cell cultures. Carnitine (10 −3 and 10 −1 M) but not DHEAS (10 −9 , 10 −8 , and 10 −7 M) increased carnitine levels within the cells. Carnitine alone and in combination with DHEAS increased palmitic acid oxidation. Both carnitine and DHEAS alone and in an additive fashion increased ALP activity and COL levels. These results demonstrate that in osteoblast-like cells in vitro, energy production can be increased by carnitine and osteoblast protein production can be increased by both carnitine and DHEAS. These data suggest that carnitine and DHEAS supplementation in the elderly may stimulate osteoblast activity and decrease age-related bone loss. Key words:Osteoblast -Carnitine -Dehydroepiandrosterone sulfate -Alkaline phosphatase -Collagen Type I.Bone loss is often divided into two broad mechanisms: (1) postmenopausal bone loss, characterized by increased osteoclast activity, and (2) age-related bone loss, characterized by decreased osteoblast activity. Osteoblast activity is dependent on energy production. Thus, it is plausible that the loss of energy production, which accompanies age, may account for decreased osteoblast activity. Most cells use both glucose and fatty acid oxidation pathways for ATP synthesis, although some cell types show a substrate preference. For instance, some studies have suggested that glucose is the major fuel substrate for bone [1,2]. However, more recent work indicates that cell populations enriched with osteoblast-like cells generate 40-80% of the energy demands through fatty acid oxidation [3]. Osteoblasts are responsible for bone formation and it follows that they maintain a high rate of ATP utilization to support the requisite protein synthesis. Cells with a high rate of protein synthesis generate ATP from fatty acid oxidation, the most efficient metabolic process for energy production [4][5][6]. Thus, modulation of fatty acid oxidation may regulate the amount of energy available for protein synthesis in osteoblasts.A number of factors are required for fatty acid oxidation. For example, carnitine is the requisite carrier for the transport of long-chain fatty acids across the inner mitochondrial membrane into...

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Section: Discussionmentioning

confidence: 95%

Carnitine and Dehydroepiandrosterone Sulfate Induce Protein Synthesis in Porcine Primary Osteoblast-Like Cells

et al. 1999

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“…In normal puberty, increase in adrenal androgen production can be detected around 6 years of age, and the phenotypic outcome consists of the development of axillary and pubic hair that occurs at w8 years of age after the increment of serum DHEAS levels over 40 ng/dl (15)(16)(17). Although the increase in adrenal androgen production is one of the hallmarks of pubertal development and normally precedes gonadarche (18), the initiation and progression of adrenarche are believed to be independent of maturation of the hypothalamicpituitary-gonadal axis and gonadal steroidogenesis (19)(20)(21).…”

Section: Discussionmentioning

confidence: 99%

Puberty in a case with novel 17-hydroxylase mutation and the putative role of estrogen in development of pubic hair

Turan¹,

Bereket²,

Güran³

et al. 2009

European Journal of Endocrinology

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Objective: 17-Hydroxylase/17,20-lyase deficiency (17OHD) results from mutations in the CYP17A1 gene, leading to failure to synthesize cortisol, adrenal androgens, and gonadal steroids. Adrenarche is a consequence of the increased production of adrenal androgens. Here, we report a case carrying novel R239Q mutation causing complete functional loss of CYP17A1, and thus absence of adrenal and gonadal sex hormone production. The patient has had unexpected pubic hair development and insufficient breast development with estrogen replacement therapy. Possible mechanisms leading to pubic hair development and breast underdevelopment are discussed. Patient and methods: A 15-year-old female born to consanguineous parents presented with the lack of full breast development and irregular menses after the age of 14 years. She had Tanner III breast development on one side, Tanner I on the other side and Tanner I pubic hair and, no axillary hair development. The serum levels of FSH, LH, and progesterone were high and, estradiol was low. The measurement of basal and ACTH-stimulated steroids was consistent with the diagnosis of 17OHD. Genetic analysis revealed novel homozygous mutation R239Q in CYP17A1 gene. Therapy with hydrocortisone was initiated and followed by the addition of conjugated estrogen. Her breast development did not improve considerably, however, pubic hair development started after estrogen treatment in spite of undetectable serum levels of androgens. Conclusion: This case study suggests that estrogen exerts a permissive effect on pubic hair development in girls, even in the presence of very low-circulating androgens, and impaired breast development might be due to estrogen/progesterone imbalance in breast tissue.

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“…DHEAS levels increased between the two study visits in all participants, consistent with previous studies demonstrating normal progression of adrenarche in children with CPP during GnRHa treatment. 29 …”

Section: Cpp Participants Sleep Study 2 (Post-treatment)mentioning

confidence: 99%

The Relationship Between Estrogen and the Decline in Delta Power During Adolescence

McHill

Klerman

Slater

et al. 2017

Sleep

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Study Objectives: During adolescence, there is a precipitous decrease in slow-wave sleep (SWS) and its spectral correlate, delta power, which may reflect cortical reorganization. The temporal association between the decrease in delta power and puberty suggests that sex steroids may initiate these changes. This association has not been previously investigated. Methods: To determine whether estrogen triggers the adolescent decline in delta power, we compared delta power in 14 girls with central precocious puberty (CPP) and 6 age-matched, prepubertal controls. Five CPP participants were re-studied 7-14 months after pubertal suppression to determine if the changes in delta power are reversible after restoring a prepubertal hormonal milieu. The change in delta power was also compared between CPP participants and five historic controls from a longitudinal polysomnographic study. Results: CPP participants (6.7-10.5 years) spent 30% of the night in SWS. Delta power (3.7 × 10 6 ± 2.7 × 10 5 µV 2 ) predominated in the first 2 non-rapid eye movement episodes and decayed exponentially (tau 0.006 minutes). Age-matched controls demonstrated similar sleep staging (24% SWS) and delta dynamics (3.3 × 10 6 ± 5.1 × 10 5 µV 2 , tau 0.004 minutes). Four out of 5 CPP participants had a significant decrease (26%) in delta power after hormone suppression (p < .05), similar to historic controls. Conclusion: Using an innovative model of girls with CPP studied before and after estrogen suppression, the effects of puberty on the decline in delta power were dissociated from those of chronologic age. The current studies suggest that increased estrogen does not cause the adolescent decline in delta power and indicate that neurodevelopmental changes per se or other factors associated with puberty drive these sleep changes.

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Adrenarche and skeletal maturation during luteinizing hormone releasing hormone analogue suppression of gonadarche.

Cited by 81 publications

References 32 publications

Carnitine and Dehydroepiandrosterone Sulfate Induce Protein Synthesis in Porcine Primary Osteoblast-Like Cells

Carnitine and Dehydroepiandrosterone Sulfate Induce Protein Synthesis in Porcine Primary Osteoblast-Like Cells

Puberty in a case with novel 17-hydroxylase mutation and the putative role of estrogen in development of pubic hair

The Relationship Between Estrogen and the Decline in Delta Power During Adolescence

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