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Examination of a possible mechanism by which anisomycin suppresses pulsatile luteinizing hormone release in
1Department of Physiology, University of Texas Health Science Center, San Antonio.
Abstract:
An initial study was performed to ascertain the effects of anisomycin, a reversible inhibitor of protein synthesis, on pulsatile luteinizing hormone (LH) release in adult, ovarietomized (OVX) rats. For this experiment, rats OVX 3-4 weeks earlier were fitted with indwelling atrial cannulae. On the next day (approximately 13.00 h), the rats received a subcutaneous injection of either 100 mg/kg body weight (BW) anisomycin or its saline vehicle. Administration of anisomycin significantly suppressed mean plasma LH levels, mean trough values, and both LH pulse frequency (saline: 6.3 pulses/3 h vs. anisomycin: 2.7 pulses/3 h) and amplitude. To determine whether anisomycin affected anterior pituitary LH responses to LH-releasing hormone (LHRH), a second experiment was performed in which saline- and anisomycin-treated OVX rats were given an intravenous injection of 10 ng/100 g BW LHRH 1.5 h later (14.30 h). Rats then were sacrificed and the anterior pituitary and brain removed. Whereas preinjection plasma LH levels were significantly lower in anisomycin-treated rats, they were significantly higher in anisomycin-treated rats 20 min after LHRH. Consequently, mean maximal increments and percent increments were significantly higher in anisomycin-treated rats. AP LH content and content of LHRH in the medial preoptic and suprachiasmatic nuclei were not influenced by anisomycin treatment. However, median eminence (ME) LHRH concentrations in anisomycin-treated rats were almost double the LHRH levels measured in control rats. A third study was conducted to assess the effects of anisomycin on basal and potassium (K+)-stimulated LHRH release from superfused ME explants.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Anisomycin, a protein synthesis inhibitor, significantly suppressed luteinizing hormone (LH) release in ovarietomized rats. However, it enhanced LH release following LHRH stimulation, indicating complex effects on the reproductive axis.
Area of Science:
- Reproductive Endocrinology
- Neuroendocrinology
Background:
- Pulsatile luteinizing hormone (LH) release is critical for reproductive function.
- Ovarietomized (OVX) rodents serve as a model to study hormonal regulation of LH secretion.
Purpose of the Study:
- To investigate the impact of anisomycin, a protein synthesis inhibitor, on pulsatile LH release in OVX rats.
- To determine if anisomycin affects anterior pituitary responsiveness to LH-releasing hormone (LHRH).
Main Methods:
- Adult OVX rats received subcutaneous anisomycin or saline vehicle.
- Plasma LH levels, pulse frequency, and amplitude were measured.
- LH and LHRH levels in plasma, anterior pituitary, and brain nuclei were analyzed post-LHRH administration.
Main Results:
- Anisomycin significantly suppressed mean LH levels, pulse frequency, and amplitude.
- Despite lower basal LH, anisomycin-treated rats showed enhanced LH release after LHRH stimulation.
- Median eminence LHRH concentrations were increased by anisomycin treatment.
Conclusions:
- Anisomycin disrupts basal pulsatile LH secretion in OVX rats.
- Anisomycin potentiates LH release in response to LHRH, suggesting altered pituitary sensitivity or hypothalamic LHRH regulation.
- Further studies are needed to elucidate the precise mechanisms underlying these effects.