Activins, dimers of inhibin beta subunits, are potent stimulators of FSH secretion in vivo and in vitro and of FSH beta mRNA expression in rat anterior pituitary cultures. In this study, we investigated the possibility that locally secreted activin B (beta B beta B) may function as an autocrine modulator of basal FSH secretion and expression based on the previous observation that beta B is expressed within gonadotropes. The incubation of cultured rat anterior pituitary cells with a m mouse monoclonal antibody specific for the activin B homodimer (MAb-activin B) significantly attenuated the basal secretion of FSH in a concentration- and time-dependent manner, without influencing LH secretion. Moreover, MAb-activin B selectively inhibited FSH beta mRNA accumulation without affecting either LH beta or alpha subunit mRNAs. The MAb-activin B completely blocked the stimulation of FSH secretion by exogenous activin B, but not by activin A, confirming its specificity. As previously shown, inhibin A and follistatin significantly suppressed basal FSH secretion in these cultures. This inhibitory effect, albeit of lower magnitude, was still evident even in the presence of the MAb-activin B which by itself suppressed basal FSH secretion. These data suggest that the secretion of activin B by the gonadotropes of the anterior pituitary may serve as an autocrine signal in the selective modulation of FSH expression and secretion. Furthermore, the inhibitory actions of inhibins and follistatins on gonadotropes may, in part, be explained by their ability to interfere with the actions of endogenous activin B.

Cisplatin, a widely used chemotherapeutic agent, induces a sensory neuropathy with selective loss of vibration sense and proprioception. Here we demonstrate that neurotrophin-3 (NT-3), a member of the nerve growth factor family of neurotrophic factors, restored to normal levels the reduced H-reflex-related sensory nerve conduction velocity induced by cisplatin in rats. NT-3 treatment corrected an abnormal cytoplasmic distribution of neurofilament protein in large sensory neurons in dorsal root ganglia and the reduction in the numbers of myelinated fibers in sural nerves caused by cisplatin. The NT-3-dependent reversal of cisplatin neurotoxicity thus suggests the possible use of NT-3 in the treatment of peripheral sensory neuropathy.

We have studied the effect of human recombinant neurotrophin-4/5 (NT-4/5) on the survival of developing PNS neurons from embryonic mice and chickens. NT-4/5 transiently supported mouse NGF-dependent trigeminal and jugular neurons at early stages of target field innervation and mouse brain-derived neurotrophic factor (BDNF)-dependent no-dose neurons during the phase of naturally occurring cell death. NT-4/5 was as potent as BDNF in supporting the survival of these neuronal populations. Surprisingly, NT-4/5 was 3 orders of magnitude less potent than BDNF as a survival factor for early chick dorsomedial trigeminal sensory neurons and did not support the survival of chick BDNF-dependent trigeminal mesencephalic or ventrolateral trigeminal sensory neurons at any of the developmental stages tested. Thus, NT-4/5 is a survival factor for certain embryonic mouse cranial sensory neurons. It is the first species-specific neurotrophin to be identified and it can discriminate at high concentrations between different BDNF-responsive chick neurons.