Ontogeny of Hypothalamic Luteinizing Hormone-Releasing Hormone (GnRH) and Pituitary GnRH Receptors in Fetal and Neonatal Rats*

Abstract

Although it is known that LH secretion starts at 17 days of gestation in the fetal rat and that this first LH release is most likely driven by hypothalamic GnRH, an earlier role for GnRH during fetal life has been postulated with the observation that presence of GnRH is important before day 13 of gestation for the differentiation of the pituitary anlage. In order to clarify the different roles of GnRH during fetal life, we have studied the first appearance of GnRH in the fetal brain, the expression of GnRH receptors in the fetal pituitary gland, and the presence of GnRH immunoreactivity within the fetal gonadotrophs. GnRH was present in the earliest brain tissue examined (12 days of gestation). From 12-17 days, GnRH content of fetal brain remained low and then increased markedly by the end of gestation. No immunoreactive GnRH-like material could be detected in rat placental tissue throughout gestation. Binding sites for GnRH were detected as early as 12 days of gestation in fetal pituitary glands. However, binding was very low until 16 days. At 17 days, Scatchard analysis indicated the presence of high affinity, low capacity binding sites [affinity constant (Ka) = 10(10) M-1]. Intracellular presence of GnRH as seen by immunocytochemistry using ultrathin sections prepared by cryoultramicrotomy was first visible at 14 days and started to increase at 16 days. LH was first detectable in the fetal pituitary by RIA at 17 days; FSH was first detectable at 21 days, and PRL at 1 day of postnatal life. Thereafter, neonatal pituitary contents of LH, FSH, and PRL increased linearly with-time, as did the number of pituitary GnRH receptors. At 10 days of postnatal life, pituitary contents of LH and FSH were significantly higher in females than in males. In summary, hypothalamic GnRH appears early in fetal life and potentially can induce differentiation of the pituitary anlage. Conversely, the presence at 15 days of gestation of specific binding sites for GnRH and of intracellular GnRH immunoreactivity in gonadotrophs indicates that the hypophysiotropic action of GnRH clearly precedes the start of LH biosynthesis.

Developmental tracing of luteinizing hormone β‐subunit gene expression using green fluorescent protein transgenic medaka (Oryzias latipes) reveals a putative novel developmental function

“…This suggests that lhb is expressed relatively late in the pituitary development, when the gross morphology of the brain and pituitary have been established and hypothalamic neurons innervate the pituitary. Thus, LH gonadotropes could require hypothalamic inputs for final gonadotrope activation similar to in sheep (Brooks et al, 1992;Szarek et al, 2008) and rat (Aubert et al, 1985) gonadotrope maturation. This is further supported by the observation that gonadotropin expression starts later than other anterior pituitary hormones in multiple fish and mammal species (Asa et al, 1988;Saga et al, 1993Saga et al, , 1999Japon et al, 1994;Laiz-Carrion et al, 2003).…”

Expression and Function of Gonadotropin-releasing Hormone (GnRH) Receptor in Human Olfactory GnRH-secreting Neurons

“…The significance of this increased GnRH production is not yet clear. It is possible that GnRH may activate pituitary gonadotropins during embryogenesis (51), thus playing a role in the organizational events of sexual differentiation (52,53). This increase in GnRH expression may also be related to guiding the direction of other migratory cells to establish the neuronal network necessary for the functioning of the GnRH cell in the central nervous system (10).…”

The masculinization of the fetus during pregnancy due to inhalation of diesel exhaust.

“…There have been few reports of adverse effects of excessive testosterone on developing male reproductive organs. In adults, testicular atrophy occurs due to the inhibition of the hypothalamic-pituitary axis affected by phamacologic doses of androgenic agents (61). Excessive testosterone may disrupt differentiation of Sertoli cells by inhibiting the development of the hypothalamic-pituitarytestis axis in fetuses.…”