Effects of
primary hypothyroidism (HYPO) on the male gonadal axis are controversial, with only scanty data on the gonadotroph cell response and no information on
GnRH tuberoinfundibular neurons, even in animal models. HYPO has been reported to variably induce
hypogonadotropic hypogonadism, a hypergonadotropic state, or to have no effects on basal levels of
pituitary gonadotropins, both in adult male rats and humans. Similarly, the exogenous administration of
GnRH to HYPO rats and humans may increase or decrease
gonadotropin secretion. Since inhibitory effects of HYPO on the
GnRH-
gonadotropin axis are reversed by replacement with L-T4, it has been suggested that
thyroid hormone (TH) may regulate tuberoinfundibular
GnRH and pituitary
gonadotropin biosynthesis and/or secretion. To shed light on this hypothesis, we conducted immunocytochemical studies on the distribution and immunostaining characteristics of hypophysiotropic
GnRH neurons, LH, PRL and
vasoactive intestinal polypeptide (VIP) immunoreactive (IR) cells in the pituitary of adult, male rats. We show that HYPO reduces IR-
GnRH in a restricted population of tuberoinfundibular perikarya and their proximal axons compared to euthyroid controls, but increases IR-VIP both in pituitary cells in direct association with LH-gonadotrophs and within IR-LH cells, itself. We propose that VIP may serve as a juxtacrine/paracrine/autocrine regulator of LH secretion and that, when
GnRH biosynthesis is reduced by HYPO,
gonadotropin secretion may be rescued by local activating effects of VIP.
Polychlorinated biphenyls (PCB), industry toxicants found in food and water, also have inhibitory effects on the gonadal axis, decreasing fertility and suppressing basal and GnRHinduced LH release in male rats. Since PCB may also exert
endocrine disruptor-dependent (EDD) effects on the thyroid axis producing a
non-thyroidal illness syndrome (NTIS) (coined EDD-NTIS), we developed a rat model of EDD-NTIS to determine whether
central hypothyroidism may contribute to the pathophysiology of PCB-induced
hypogonadism. On the basis of preliminary animal data, we speculate that one of the mechanisms for Partial
Androgen Deficiency of the Aging Male may involve
central hypothyroidism and EDD-NTIS, resulting in inhibition of the
GnRH-gonadotroph axis.