The hypothalamus resides at the base of the brain, constituting the floor and inferior- lateral walls of the third ventricle. The hypothalamus is in volved with a wide variety of biological processes including growth and development, energy homeostasis, weight maintenance, responses to stress, and reproduction. With regard to reproduction, the cell bodies of some 1000– 1500 GnRH- secreting neurons are diffusely located throughout the preoptic area and the infundibular nucleus (the arcuate nucleus in lower mammalian species) (Figure 1). Selective destruction of the arcuate nucleus in mature female monkeys leads to severe hypogonadotropic hypogonadism, suggesting that normal gonadotropin secretion is particularly dependent on the population of GnRH neurons residing in the infundibular (arcuate) nucleus.
Fig1. Anatomic foundations for GnRH neuron- gonadotrope interactions. GnRH neuron cell bodies reside in the infundibular nucleus (part of the mediobasal hypothalamus) and the preoptic area. GnRH neurons processes (dendrons) extend to the median eminence (also part of the mediobasal hypothalamus), where GnRH is released into the hypophyseal portal system. GnRH subsequently travels to the anterior pituitary where it interacts with gonadotrope cells. Adapted with permission from Johnson and Everitt’s Essential reproduction, ed 6. Blackwell Publishing, 2007, Fig. 6.4.
GnRH neurons extend processes through the tuberoinfundibular tract to the median eminence at the base of the third ventricle. GnRH neuron fibres have been called ‘dendrons’ because, in mice, they demonstrate characteristics of both axons and dendrites, including functional synaptic inputs throughout the length of the fibre. Bursts of GnRH neuronal firing result in the release of GnRH into an extensive capillary network located within the median eminence— the proximal portion of the hypophyseal portal system. GnRH release may also be influenced by interactions with other cell populations in the median eminence. For example, projections from tanycytes— specialized ependymal cells lining the third ventricle— can reduce GnRH release by enveloping and physically isolating GnRH nerve terminals.
The hypophyseal portal circulation represents the anatomical and functional connection between the median eminence and cells of the anterior pituitary. The superior hypophyseal artery feeds the capillary network within the median eminence. This network drains into sinusoids that coalesce to form the hypophyseal portal veins, which traverse the pituitary stalk and constitute the chief blood supply for the anterior pituitary.
The pituitary gland is located within a saddle- like structure of the sphenoid bone (the sella turcica), and it is connected to the base of the hypothalamus by the pituitary stalk. The anterior lobe (pars distalis) of the pituitary contains specialized cells (gonadotropes) that produce luteinizing hormone (LH) and follicle- stimulating hormone (FSH). GnRH binds to GnRH receptors on the cell sur face of gonadotropes, initiating an intracellular cascade that results in the synthesis and secretion of LH and FSH. These gonadotropins are released directly into the systemic circulation and ultimately direct ovarian follicular development, cyclic ovulation, and cyclic changes of ovarian sex steroid production.
