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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

Developmental Endocrinology Branch, National Institute of Child Health and Human Development Bethesda, Maryland 20892
Nuclear Medicine Department Bethesda, Maryland 20892
National Center of Research Resources Bethesda, Maryland 20892
the National Institute of Allergy and Infectious Diseases Bethesda, Maryland 20892
National Institutes of Health Bethesda, Maryland 20892
the Southern Research Institute, Control Release Division Birmingham, Alabama 35255

Address requests for reprints to: Dr. Linda Liu, Building 10, Room 10N-262, National Institutes of Health, Bethesda, Maryland 20892.

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 longacting 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.

Received November 21, 1990.

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