Sexual maturation of male rats treated postnatally with a gonadotrophin-releasing hormone antagonist

Abstract

Postnatal secretion of gonadotrophin by male rats was inhibited by a potent gonadotrophin-releasing hormone (GnRH) antagonist analogue (N-Ac-4-Cl-D-Phe1,4-Cl-D-Phe2,D-Trp3,D-Phe6,des-Gly10-GnRH-D-al anylamide; Org 30039; 2 mg/kg s.c. twice daily) on days 1-5, 6-10, 11-15 or 16-20 of life. The onset of puberty was determined by monitoring the separation of the preputium from the glans penis, i.e. balano-preputial separation (BPS). Rats treated on days 1-5 matured normally, whereas all treatments between days 6 and 20 delayed BPS (P less than 0.01). In adult rats (between 110 and 160 days of age), testis weights were reduced by 21-35% (P less than 0.01) in groups treated between days 1 and 15, although weights of the accessory sex glands were normal. Testicular FSH receptors were decreased by 31-47% (P less than 0.01) in all treatment groups, whereas the LH receptor content was decreased only in rats treated between days 1 and 5 (18%; P less than 0.05) and prolactin receptor content decreased only in rats treated up to day 10 (31-33%; P less than 0.01). Concentrations of serum testosterone, LH and FSH, and pituitary contents of LH and FSH were unaffected by neonatal treatment with Org 30039. Animals treated with Org 30039 had reduced fertility which was most pronounced (88%; P less than 0.01) in rats treated between days 1 and 5. However, motile sperm were detectable in the cauda epididymis of the infertile rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Alteration of pituitary hormone-immunoreactive cell populations in rat offspring after maternal dietary exposure to endocrine-active chemicals

“…*P<0.05, **P<0.01, indicating statistical differences between the two groups testicular weights at prepubertal necropsy (Table 1). Both LH and FSH play roles in testicular development (Huhtaniemi 1995), and male rats treated neonatally with a gonadotropin-releasing hormone (GnRH) antagonist exhibit delay in the onset of puberty (Kolho et al 1988). Therefore, the decrease in our pituitary cells expressing LH or FSH may be a feature of retarded postnatal maturation of the hypothalamic-pituitary axis, although a causal influence cannot be concluded at present.…”

Ovarian Tumorigenesis in Mice Transgenic for Murine Inhibin α Subunit Promoter-Driven Simian Virus 40 T-Antigen: Ontogeny, Functional Characteristics, and Endocrine Effects1

“…Serum FSH was measured by a double-antibody RIA method (National Institute of Diabetes and Digestive and Kidney Diseases; Bethesda, MD), where the hormone preparation was radioiodinated with sodium [ 125 I]iodide (IMS 300; Amersham, Buckinghamshire, UK) using the chloramine-T method, as described earlier [24]. Serum LH was measured by a supersensitive immunofluorometric assay (Delfia; Wallac OY, Turku, Finland), developed in our laboratory for rat LH [25].…”

Suppression of pituitary-testis function in rats treated neonatally with a gonadotrophin-releasing hormone agonist and antagonist: acute and long-term effects

“…In our previous studies on acute and long-term effects of GnRH antagonist treatment of immature rats, a different analogue, Org 30039, was used at a dose of 2 mg/kg body weight s.c. twice daily (Huhtaniemi et al 1985ft, 1986Kolho et al 1988). The present analogue clearly suppressed pituitarygonadal function at a single dose of 2 mg/kg per day.…”

“…Interestingly, despite the decline of pituitary FSH neonatally, INTRODUCTION Perinatal pituitary-gonadal activity is essential for later sexual maturation in mammals, but details of these actions are still poorly understood (Gorski, 1979;Huhtaniemi, Warren & Catt, 1984;Sachs & Meisel, 1988). Gonadotrophin-releasing hormone (GnRH) agonists and antagonists provide powerful tools for modification of the activity of the pituitarygonadal axis (Labrie, Bélanger & Dupont, 1984; Huhtaniemi, Nevo, Amsterdam & Naor, 1986; Kolho, Nikula & Huhtaniemi, 1988). In the sexually mature animal, administration of GnRH agonist analogues results in a short stimulation of gonadotrophin secretion; thereafter the cellular responses are desensitized and gonadotrophin secretion is sup¬ pressed (Belchetz, Plant, Nakai et al 1978;Catt, Harwood, Aquilera & Dufau, 1979; Clayton .…”

“…Blockade of pituitary-gonadal function by antagonist treatment in the neonatal rat has been shown to delay sexual maturation and permanently affect pituitary and testis function (Huhtaniemi et al 1986;Kolho et al 1988). These findings prompted us to compare in detail the acute and long-term effects of suppression of pituitary function by a GnRH agonist and antagonist analogue administered during the neonatal period.…”