Effects of pituitary-testicular axis suppression in utero and during the early neonatal period with a long-acting luteinizing hormone-releasing hormone analog on genital development, somatic growth, and bone density in male cynomolgus monkeys in the first 6 months of life

Linda Liu, Audrey M. Cristiano, Janice L. Southers, James C. Reynolds, John Bacher, Garland Brown, Richard M. Gilley, Thomas R. Tice, Steven M. Banks, Donald (Lynn) Loriaux, Fernando Cassorla

Research output: Contribution to journalArticle

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Abstract

The specific role of late fetal and early neonatal gonadotropins and/or sex steroids on genital development, linear growth, and bone mass accretion remains unclear. To investigate this, we attempted to selectively suppress pituitary-testicular activation from midgestation through early infancy with a long-acting LHRH agonist (LHRHA), D-Trp6,Pro9-NEt-LHRH, in microspheres. The agonist was injected sc on days 72-81 in utero, on day 1 of life, and 3 months postnatally in male cynomolgus monkeys. Control animals were treated with placebo. We then examined the consequences of such an intervention in the first 6 months of life. In the LHRHA-treated animals, marked suppression of plasma testosterone and gonadotropin levels were evident in the first 3 months of life compared to control values. The mean testicular volumes of the LHRHA group were significantly lower at birth and in the first 2 months of life than those of the placebo group (P <0.05). However, by 4 months of age, the mean testicular volumes of the two groups were comparable. Similarly, the mean stretched phallic lengths of the LHRH∼A group were significantly lower than those of the placebo group throughout the first 6 months of life (P <0.05). By contrast, LHRHA treatment had no effect on somatic growth, as mean body weights, total body lengths, and trunk lengths of the two groups were similar over the first 6 months of life. Mean bone widths and densities of the distal third of the left radius and the left midfemur were similar in the two groups at 1 and 6 months of life. We conclude that pituitary-testicular axis suppression with a long-acting LHRHA in utero and during early infancy results in markedly stunted penile and testicular growth without affecting general somatic growth and bone density of appendicular cortical bone in the cynomolgus monkey in the first 6 months of life. Thus, an intact fetal and neonatal pituitary-testicular axis is critical for normal genital growth. However, the sex steroid requirement for maintenance of bone mineral content of appendicular cortical bone may be lower than that necessary for normal genital development.

Original languageEnglish (US)
Pages (from-to)1038-1043
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume73
Issue number5
StatePublished - Nov 1991
Externally publishedYes

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Macaca fascicularis
Growth and Development
Gonadotropin-Releasing Hormone
Bone Density
Bone
Gonadotropins
Bone Development
Placebos
Growth
Animals
Steroids
Birth Order
Microspheres
Minerals
Testosterone
Chemical activation
Plasmas
Body Weight
Maintenance

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Effects of pituitary-testicular axis suppression in utero and during the early neonatal period with a long-acting luteinizing hormone-releasing hormone analog on genital development, somatic growth, and bone density in male cynomolgus monkeys in the first 6 months of life. / Liu, Linda; Cristiano, Audrey M.; Southers, Janice L.; Reynolds, James C.; Bacher, John; Brown, Garland; Gilley, Richard M.; Tice, Thomas R.; Banks, Steven M.; Loriaux, Donald (Lynn); Cassorla, Fernando.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 73, No. 5, 11.1991, p. 1038-1043.

Research output: Contribution to journalArticle

Liu, Linda ; Cristiano, Audrey M. ; Southers, Janice L. ; Reynolds, James C. ; Bacher, John ; Brown, Garland ; Gilley, Richard M. ; Tice, Thomas R. ; Banks, Steven M. ; Loriaux, Donald (Lynn) ; Cassorla, Fernando. / Effects of pituitary-testicular axis suppression in utero and during the early neonatal period with a long-acting luteinizing hormone-releasing hormone analog on genital development, somatic growth, and bone density in male cynomolgus monkeys in the first 6 months of life. In: Journal of Clinical Endocrinology and Metabolism. 1991 ; Vol. 73, No. 5. pp. 1038-1043.
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abstract = "The specific role of late fetal and early neonatal gonadotropins and/or sex steroids on genital development, linear growth, and bone mass accretion remains unclear. To investigate this, we attempted to selectively suppress pituitary-testicular activation from midgestation through early infancy with a long-acting LHRH agonist (LHRHA), D-Trp6,Pro9-NEt-LHRH, in microspheres. The agonist was injected sc on days 72-81 in utero, on day 1 of life, and 3 months postnatally in male cynomolgus monkeys. Control animals were treated with placebo. We then examined the consequences of such an intervention in the first 6 months of life. In the LHRHA-treated animals, marked suppression of plasma testosterone and gonadotropin levels were evident in the first 3 months of life compared to control values. The mean testicular volumes of the LHRHA group were significantly lower at birth and in the first 2 months of life than those of the placebo group (P <0.05). However, by 4 months of age, the mean testicular volumes of the two groups were comparable. Similarly, the mean stretched phallic lengths of the LHRH∼A group were significantly lower than those of the placebo group throughout the first 6 months of life (P <0.05). By contrast, LHRHA treatment had no effect on somatic growth, as mean body weights, total body lengths, and trunk lengths of the two groups were similar over the first 6 months of life. Mean bone widths and densities of the distal third of the left radius and the left midfemur were similar in the two groups at 1 and 6 months of life. We conclude that pituitary-testicular axis suppression with a long-acting LHRHA in utero and during early infancy results in markedly stunted penile and testicular growth without affecting general somatic growth and bone density of appendicular cortical bone in the cynomolgus monkey in the first 6 months of life. Thus, an intact fetal and neonatal pituitary-testicular axis is critical for normal genital growth. However, the sex steroid requirement for maintenance of bone mineral content of appendicular cortical bone may be lower than that necessary for normal genital development.",
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AU - Liu, Linda

AU - Cristiano, Audrey M.

AU - Southers, Janice L.

AU - Reynolds, James C.

AU - Bacher, John

AU - Brown, Garland

AU - Gilley, Richard M.

AU - Tice, Thomas R.

AU - Banks, Steven M.

AU - Loriaux, Donald (Lynn)

AU - Cassorla, Fernando

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N2 - The specific role of late fetal and early neonatal gonadotropins and/or sex steroids on genital development, linear growth, and bone mass accretion remains unclear. To investigate this, we attempted to selectively suppress pituitary-testicular activation from midgestation through early infancy with a long-acting LHRH agonist (LHRHA), D-Trp6,Pro9-NEt-LHRH, in microspheres. The agonist was injected sc on days 72-81 in utero, on day 1 of life, and 3 months postnatally in male cynomolgus monkeys. Control animals were treated with placebo. We then examined the consequences of such an intervention in the first 6 months of life. In the LHRHA-treated animals, marked suppression of plasma testosterone and gonadotropin levels were evident in the first 3 months of life compared to control values. The mean testicular volumes of the LHRHA group were significantly lower at birth and in the first 2 months of life than those of the placebo group (P <0.05). However, by 4 months of age, the mean testicular volumes of the two groups were comparable. Similarly, the mean stretched phallic lengths of the LHRH∼A group were significantly lower than those of the placebo group throughout the first 6 months of life (P <0.05). By contrast, LHRHA treatment had no effect on somatic growth, as mean body weights, total body lengths, and trunk lengths of the two groups were similar over the first 6 months of life. Mean bone widths and densities of the distal third of the left radius and the left midfemur were similar in the two groups at 1 and 6 months of life. We conclude that pituitary-testicular axis suppression with a long-acting LHRHA in utero and during early infancy results in markedly stunted penile and testicular growth without affecting general somatic growth and bone density of appendicular cortical bone in the cynomolgus monkey in the first 6 months of life. Thus, an intact fetal and neonatal pituitary-testicular axis is critical for normal genital growth. However, the sex steroid requirement for maintenance of bone mineral content of appendicular cortical bone may be lower than that necessary for normal genital development.

AB - The specific role of late fetal and early neonatal gonadotropins and/or sex steroids on genital development, linear growth, and bone mass accretion remains unclear. To investigate this, we attempted to selectively suppress pituitary-testicular activation from midgestation through early infancy with a long-acting LHRH agonist (LHRHA), D-Trp6,Pro9-NEt-LHRH, in microspheres. The agonist was injected sc on days 72-81 in utero, on day 1 of life, and 3 months postnatally in male cynomolgus monkeys. Control animals were treated with placebo. We then examined the consequences of such an intervention in the first 6 months of life. In the LHRHA-treated animals, marked suppression of plasma testosterone and gonadotropin levels were evident in the first 3 months of life compared to control values. The mean testicular volumes of the LHRHA group were significantly lower at birth and in the first 2 months of life than those of the placebo group (P <0.05). However, by 4 months of age, the mean testicular volumes of the two groups were comparable. Similarly, the mean stretched phallic lengths of the LHRH∼A group were significantly lower than those of the placebo group throughout the first 6 months of life (P <0.05). By contrast, LHRHA treatment had no effect on somatic growth, as mean body weights, total body lengths, and trunk lengths of the two groups were similar over the first 6 months of life. Mean bone widths and densities of the distal third of the left radius and the left midfemur were similar in the two groups at 1 and 6 months of life. We conclude that pituitary-testicular axis suppression with a long-acting LHRHA in utero and during early infancy results in markedly stunted penile and testicular growth without affecting general somatic growth and bone density of appendicular cortical bone in the cynomolgus monkey in the first 6 months of life. Thus, an intact fetal and neonatal pituitary-testicular axis is critical for normal genital growth. However, the sex steroid requirement for maintenance of bone mineral content of appendicular cortical bone may be lower than that necessary for normal genital development.

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