Effect of Neonatal Androgen on the Activity of Peptidases in the Rat Brain Inactivating Luteinizing Hormone-Releasing Hormone

Abstract

The activity of peptidase enzymes in different brain areas inactivating luteinizing hormone-releasing hormone (LH-RH) was investigated in normal male and female rats and female rats treated neonatally with androgen. Of the two fractions containing peptidase activity, changes were found only in the supernatant (soluble/cytoplasmic) fraction and were restricted to the hypothalamus and cortex. In both these brain areas, peptidase activity was considerably higher in androgen-treated than in normal female rats; there was no significant difference between activity in male rats and the androgen-treated female rats. These findings indicate that neonatal androgen produces masculinization of the mechanisms responsible for LH-RH inactivation in the hypothalamus which may reflect changes observed elsewhere in gonadotropin secretion in androgen-treated female rats. The changes in peptidase activity in the cortex may infer that sexual differentiation of the brain under the influence of androgen is not limited to the hypothalamus and can be manifested at extrahypothalamic sites within the central nervous system.

Effects of Androgen Administered to Neonatal Male Rats on Hypophyseal Gonadotropin Content, Secretion and Response to LHRH at Adulthood

“…Such lesions might occur at various levels of neural organization, e.g. : (1) 'chemo-lesions', such as those involved in synthesis or degradation of neurotransmit ters [16] or LHRH (indeed, elevated activity of an LHRH inactivating peptidase occurs following neonatal androgenization in fe males [19]); (2) 'organizational lesions' re sulting in abnormal neuronal connections at critical sites [20,21], such as the arcuate nucleus of the medial basal hypothalamus or regions which project LHRH fibers to the arcuate nucleus [22], Such lesions in LHRH pulse generation, with consequent inade quate induction of pituitary LHRH recep tors [10,11], would ultimately result in de creased capacities for accumulation and se cretion of gonadotropins, as observed in this study, and suppression of testicular matura tion, as previously reported [1]. Indeed, rats receiving LHRH antiserum postnatally [23] and the mutant LHRH-deficient mouse [24] manifest deficient testicular maturation, similar to that observed following neonatal androgenization [1],…”

Gonadal steroids regulate immunoreactive tachykinin in the ventromedial nucleus of the rat hypothalamus

“…The ventrolateral subdivision (VMHv1) is a major neural target for estrogen (Pfaff and Keiner, 1973) and estrogen implants in the VMHvl are sufficient to restore lordosis behavior in female rats made nonreceptive by ovariectomy (Rubin and Barfield, 1980). Estrogen activates lordosis through both genomic and nongenomic mechanisms (McEwen et al, 1990) and some of the gene products that may be relevant to lordosis include peptides (Harlan, 19881, receptors (Akesson et al, 1987;O'Connor et al, 1988;Coirini et al, 1989) and enzymes involved in inactivation of transmitters and neuromodulators (Griffiths et al, 1976;Luine and Rhodes, 1983).…”

Molecular Polymorphism of Native Gonadotropin-Releasing Hormone (GnRH) Is Restricted to Mammalian GnRH and [Hydroxyproline⁹] GnRH in the Developing Rat Brain

“…To our knowledge, developing PEP activity has not been studied so far in females. The GnRH-degrading system is known to be under sex steroid control [43,44,45] and neonatal female rats treated with androgen show higher peptidase activity inactivating mGnRH than normal animals [46]. This control mechanism may be of physiological interest in male rats, in which the plasma testosterone level increases just before birth and during the first postnatal days [47].…”