ANTIANDROGEN MICROIMPLANTS INTO THE ROSTRAL MEDIAL PREOPTIC AREA DECREASE GAMMA-AMINOBUTYRIC ACIDERGIC NEURONAL-ACTIVITY AND INCREASE LUTEINIZING-HORMONE SECRETION IN THE INTACT MALE-RAT
Dr. Grattan et al., ANTIANDROGEN MICROIMPLANTS INTO THE ROSTRAL MEDIAL PREOPTIC AREA DECREASE GAMMA-AMINOBUTYRIC ACIDERGIC NEURONAL-ACTIVITY AND INCREASE LUTEINIZING-HORMONE SECRETION IN THE INTACT MALE-RAT, Endocrinology, 137(10), 1996, pp. 4167-4173
gamma-Aminobutyric acid (GABA)ergic neurons terminating in the rostral
hypothalamus are stimulated by testosterone. To investigate whether t
his action is mediated locally through androgen receptors in the rostr
al hypothalamus, bilateral microcannulas (28 gauge) containing the and
rogen receptor antagonist, hydroxyflutamide (HF), were stereotaxically
implanted into the rostral medial preoptic area (rMPA) just dorsal to
the major population of GnRH cell bodies. Two days later, blood sampl
es were collected for assay of LH, and animals were killed for determi
nation of GABAergic neuronal activity in tissue dissected from the sit
e of the implanted cannulas. Animals were decapitated either without t
reatment or 60 min after inhibition of GABA degradation by aminooxyace
tic acid (100 mg/kg, ip). The rate of GABA accumulation in the tissue
after aminooxyacetic acid treatment was used as a measure of GABA turn
over. Levels of messenger RNA for both forms of glutamic acid decarbox
ylase (GAD(65) and GAD(67)), the rate-limiting enzyme responsible for
GABA synthesis also were measured by a microlysate ribonuclease protec
tion assay. LH levels were significantly increased (1.8-fold) in HF-tr
eated animals compared with controls. In the MPA, beneath the implant
cannulas, GABA turnover was significantly reduced in HF-treated rats.
There was no effect of treatment in the frontal cortex, which was used
as a control region. Surprisingly, levels of messenger RNA for both G
AD(65) and GAD(67) were significantly increased in HF-treated rats. Th
e results indicate that GABAergic neurons terminating in the rostral h
ypothalamus are tonically stimulated by testosterone acting by means o
f androgen receptors localized in this region. These findings support
the working hypothesis that androgen-sensitive GABAergic neurons in th
e rMPA mediate the negative feedback action of testosterone on GnRH se
cretion in the male rat.