Summary. Homogenates of normal human muscle showed cathepsin activity over a wide pH range, with peaks at pH 3.9 and 6.6. Of various proteins tested, denatured myoglobin was the best substrate at pH 4; some proteins depressed activity. In human dystrophic muscle (Duchenne) there was increased cathepsin activity (based on non-collagen protein) in the acid, neutral and alkaline range.

The release of GnRH from nerve terminals in the median eminence into the portal vessels is influenced by factors in the internal and external environment of the animal. In the former category are the gonadal steroid hormones oestrogen and progesterone which alter the characteristics of GnRH secretion during the oestrous and seasonal cycles. These cannot exert their actions directly on the GnRH neurones as they do not possess hormone receptors. Therefore, some other steroid-sensitive neuronal system must relay this information to the GnRH neurones. Gamma amino-butyric acid (GABA) neurones are good candidates for this role as they contain steroid hormone receptors and synapse on GnRH neurones. Recent studies in ewes have sought to identify a role for GABA in mediating the actions of both oestrogen and progesterone on GnRH release. The technique of microdialysis was used to monitor GABA concentrations in areas containing GnRI-I cell bodies during the oestrogen-induced surge of GnRH and during progesterone negative feedback. Concentrations of this inhibitory neurotransmitter have been shown to fall in the former situation where GnRH release is being stimulated, but to be increased when progesterone is depressing GnRH release. GABA may also be important in mediating the seasonal switch in the negative feedback actions of oestradiol. During the anoestrous season, when oestradiol is a potent inhibitor of GnRH secretion, specific GABA receptor antagonists can stimulate neurohormone release, an action that is not observed in the breeding season when oestrogen is much less potent.

Exposure of the sheep fetus to testosterone from day 30 to day 90 of a 147 day gestation causes the neurones that control GnRH secretion, the GnRH neuronal network, to become organized in a sex-specific manner. After androgen exposure in utero, GnRH neurones are activated in a sexually differentiated pattern by gonadal steroid hormones. Specifically, follicular phase concentrations of oestrogen trigger a GnRH 'surge' in ewes, but not in rams or females treated with androgen during fetal life. Furthermore, progesterone is a less potent inhibitor of GnRH release in rams or females treated with androgen during fetal life. The reasons for the sexual differentiation of these steroid feedback mechanisms probably reside in a dimorphism in steroid-sensitive neural inputs to GnRH neurones. The density of neurones containing oestrogen receptor a is sexually differentiated in areas of the ovine brain that are known to be involved in the steroidal regulation of GnRH. Furthermore, neurones in these regions are activated in a gender-specific pattern. A determination of the neural phenotype of these steroid-sensitive cells will form a basis for understanding the mechanisms by which the GnRH neuronal network is organized and activated in a sexually differentiated manner.