Hypothalamic input is required for development of normal numbers of thyrotrophs and gonadotrophs, but not other anterior pituitary cells in late gestation sheep

Abstract

To evaluate the hypothalamic contribution to the development of anterior pituitary (AP) cells we surgically disconnected the hypothalamus from the pituitary (hypothalamo-pituitary disconnection, HPD) in fetal sheep and collected pituitaries 31 days later. Pituitaries (n = 6 per group) were obtained from fetal sheep (term = 147 ± 3 days) at 110 days (unoperated group) of gestation and at 141 days from animals that had undergone HPD or sham surgery at 110 days. Cells were identified by labelling pituitary sections with antisera against the six AP hormones. Additionally, we investigated the colocalization of glycoprotein hormones. The proportions of somatotrophs and corticotrophs were unchanged by age or HPD. Lactotrophs increased 80% over time, but the proportion was unaffected by HPD. Thyrotrophs, which were unaffected by age, increased 70% following HPD. Gonadotrophs increased with gestational age (LH+ cells 55%; FSH+ cells 19-fold), but this was severely attenuated by HPD. We investigated the possible existence of a reciprocal effect of HPD on multipotential glycoprotein-expressing cells. Co-expression of LH and TSH was extremely rare (< 1%) and unchanged over the last month of gestation or HPD. The increase of gonadotrophs expressing FSH only or LH and FSH was attenuated by HPD. Therefore, the proportions of somatotrophs, lactotrophs and corticotrophs are regulated independently of hypothalamic input in the late gestation fetal pituitary. In marked contrast, the determination of the thyrotroph and gonadotroph lineages over the same time period is subject to complex mechanisms involving hypothalamic factors, which inhibit differentiation and/or proliferation of thyrotrophs, but stimulate gonadotrophs down the FSH lineage. Development of a distinct population of gonadotrophs, expressing only LH, appears to be subject to alternative mechanisms. The anterior pituitary is a highly heterogeneous organ composed of a variety of cells located throughout the gland. The process by which the individual secretory cells differentiate and proliferate during development is largely unknown. Considerable progress has been made in understanding the role played by transcription factors, but we still know relatively little about the input of the fetal hypothalamus in pituitary cell development. After birth, hypothalamic factors are critical in regulating anterior pituitary (AP) function, but the role played before birth remains largely unknown.Recent studies suggest that the timely expression of various transcription factors is wholly responsible for the composition of the AP, independent of the hypothalamus (Dasen & Rosenfeld, 1999Melmed, 2003). A number of experiments in genetically engineered mice are consistent with this view. For example, corticotrophin-releasing hormone (CRH) receptor knockout mice (Timpl et al. 1998) and thyrotrophin-releasing hormone (TRH) knockout mice have a normal complement of all pituitary cells (Shibusawa et al. 2000), clearly suggesting that these two hypothalamic factors are not required for normal...

Embryonic gonadotropin-releasing hormone signaling is necessary for maturation of the male reproductive axis

“…Our data show that FSH+ gonadotrope development is arrested in absence of embryonic GnRH signaling. Consistent with this, hypothalamic input is required for normal development of FSH+ gonadotropes in sheep (20). The residual FSH+ cells in GRIC/R26-DTA mice fail to initiate GnRHR and to up-regulate FSHβ expression.…”

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

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