Lesions in the hypothalamus after active immunisation against GnRH in the pig.

The terminals of the hypothalamic gonadotrophin hormone-releasing hormone (GnRH) neurons are located within the median eminence and thereby extend beyond the protection of the blood-brain barrier. Thus, these terminals may be subjected to direct autoimmune action in animals that are actively immunised against GnRH. Boars (male pigs) (n = 108) were actively immunised against GnRH by two successive injections with synthetic GnRH, covalently coupled to KLH and dissolved in CFA or IFA. They were killed at 26 weeks of age. Immunised boars were selected on the basis of the resultant testes size, which indicates the effectiveness of the immunisation. The hypothalami of 25 selected animals were studied by histological and immunocytochemical techniques and compared with the hypothalami of three sham- and nine control animals. In the immunised animals, changes in the GnRH system had taken place. These comprised dystrophy of the perikarya and a sharp decrease of the GnRH immunocytochemical reactivity in the terminals within the median eminence. In addition, various degrees of inflammatory reactions were present, particularly within the median eminence. These consisted of tissue disruption by edema, collapse of the capillaries, fibrosis and infiltration with fibroblasts. In addition, accumulations of neurosecretum within the median eminence in combination with hypertrophy of magnocellular neurons within the hypothalamus were present. The reactions were restricted to the median eminence and did not involve other neurohemal organs or other parts of the hypothalamus. A correlation could be established between the incidence of the lesions and the effectiveness of the GnRH autoimmunity (as indicated by the size and endocrine function of the gonads and the anti-GnRH titres). Changes in extra- and intracellular IgG immunocytochemical reactivity within the median eminence indicated the involvement of IgG. The effects were absent from control and sham vaccinated animals and after vaccinations with other compositions of the vaccine. Thus, hypothalamic lesions have been observed in this selected group of animals, vaccinated against GnRH with this particular vaccine.

The supraoptic nucleus in the pig hypothalamus: postnatal development and the effect of gonadal steroids.

Postnatal development of the supraoptic nucleus (SON) in the pig hypothalamus was studied morphometrically. The volume of the SON increased from 6.2 +/- 0.45 (S.E.M.) mm3 at 7 weeks postnatally to 18.5 +/- 1.35 mm3 at 2.5 years of age. A sex difference was found at the development point when the SON volume increased, with earlier SON enlargement in males. This sex difference was 30% at 30 weeks and 50% at 1 year of age. At 2.5 years of age no difference in volume was apparent between the sexes. The number of SON neurones was similar for all age groups concerned (43,500 +/- 1475), except for the 2.5-year-old females where 40% more were found (55,500 +/- 3285). No significant difference was found in neurone number between gonadectomized and sham-operated animals, but the operation caused a 30% reduction in the number of neurones and SON volume. Testosterone supplementation following gonadectomy, during the first 4 weeks postnatally, resulted in sexual dimorphism, the males having more SON neurones than the females. The volume showed only a trend in the same direction. Testosterone supplementation at other ages did not result in any difference when compared with controls. The results of this study show that the postnatal development of the SON of the pig is sexually dimorphic, and that it continues after puberty in females. In contrast to the vasopressin- and oxytocin-containing nucleus, the development of the SON was not influenced by gonadectomy and only slightly by gonadal steroids.

Influence of gonadectomy and testosterone supplementation on the postnatal development of the vasopressin and oxytocin-containing nucleus of the pig hypothalamus.

We have studied the effects of gonadectomy and testoterone supplementation on the development of the vasopressin- and oxytocin-containing nucleus (VON) of the pig hypothalamus that shows a decrease in neuron number during the first weeks postnatally, followed by an increase during puberty. Neonatal gonadectomy caused a 2.5-fold increase in VON volume and neuron number in males and 3-fold in females at the age of 16 weeks, the onset of puberty. However, the difference between gonadectomized and nongonadectomized animals disappeared after puberty (38 weeks). Testosterone replacement from 16 weeks onwards induced a decrease in neuron number and volume of the VON. The present study indicates that the development of the VON is influenced by gonadal steroids although it seems improbable that these hormones affect the VON directly.